%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Elwira Smolińska, Marta Moskot, Joanna Jakóbkiewicz-Banecka, Grzegorz Węgrzyn, Bogdan Banecki, Aneta Szczerkowska-Dobosz, Dorota Purzycka-Bohdan, Magdalena Gabig-Cimińska
Molecular action of isoflavone genistein in the human epithelial cell line HaCaT
www.plosone.org
www.plosone.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 13 0 R/Annots 14 0 R/Contents 15 0 R/TrimBox[0 0 612 792]>>
endobj
14 0 obj
[16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R]
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref001)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref006)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref007)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref004)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref008)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref009)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref010)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref011)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref012)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref016)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref017)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref018)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref019)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref020)>>
endobj
30 0 obj
<>/Border[0 0 0]/A 32 0 R>>
endobj
32 0 obj
<>
endobj
31 0 obj
<>/Border[0 0 0]/A 33 0 R>>
endobj
33 0 obj
<>
endobj
15 0 obj
[34 0 R 35 0 R 36 0 R 37 0 R 38 0 R 39 0 R 40 0 R 41 0 R 42 0 R 43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R 49 0 R 50 0 R 51 0 R]
endobj
34 0 obj
<>stream
q
0.83 0.64 0.02 0 k
301.8331 680.315 m
306.5953 680.315 l
h
f*
311.7543 680.315 m
316.5165 680.315 l
h
f*
281.5937 628.3276 m
286.3559 628.3276 l
h
f*
366.4063 602.3055 m
371.1685 602.3055 l
h
f*
506.7213 563.3008 m
511.4835 563.3008 l
h
f*
453.4866 537.3354 m
458.2488 537.3354 l
h
f*
462.6709 537.3354 m
472.1953 537.3354 l
h
f*
291.7984 498.3307 m
301.2661 498.3307 l
h
f*
260.1071 407.3386 m
269.6315 407.3386 l
h
f*
274.7906 407.3386 m
284.315 407.3386 l
h
f*
419.074 307.1055 m
428.5984 307.1055 l
h
f*
338.7969 164.126 m
348.2646 164.126 l
h
f*
352.7433 164.126 m
362.2677 164.126 l
h
f*
285.222 138.1039 m
294.7465 138.1039 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(been)Tj
2.1203 0 Td
(made)Tj
2.4264 0 Td
(in)Tj
1.0375 0 Td
(clarifying)Tj
3.9855 0 Td
(the)Tj
1.4683 0 Td
(molecular)Tj
4.2179 0 Td
(pathogenesis)Tj
5.3518 0 Td
(of)Tj
1.0148 0 Td
(psoriasis.)Tj
3.8948 0 Td
(Transcriptomic)Tj
6.4402 0 Td
(analyses)Tj
3.481 0 Td
(have)Tj
-35.4385 -1.3039 Td
(been)Tj
2.1203 0 Td
(widely)Tj
2.8232 0 Td
(used)Tj
2.0636 0 Td
(in)Tj
1.0319 0 Td
(recent)Tj
2.7099 0 Td
(years)Tj
2.262 0 Td
(to)Tj
1.0261 0 Td
(identify)Tj
3.2995 0 Td
(differentially)Tj
5.3008 0 Td
(expressed)Tj
4.0932 0 Td
(genes)Tj
2.4434 0 Td
(\(DEGs\))Tj
3.2825 0 Td
(associated)Tj
-32.4564 -1.2982 Td
(with)Tj
1.9955 0 Td
(psoriasis)Tj
3.668 0 Td
(pathology)Tj
4.1783 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(].)Tj
2.5908 0 Td
(While)Tj
2.6532 0 Td
(there)Tj
2.2621 0 Td
(is)Tj
0.8504 0 Td
(now)Tj
1.9559 0 Td
(increasing)Tj
4.3313 0 Td
(insight)Tj
2.9536 0 Td
(into)Tj
1.8426 0 Td
(the)Tj
1.4683 0 Td
(genes)Tj
2.4434 0 Td
(conferring)Tj
-33.1934 -1.2983 Td
(disease)Tj
3.016 0 Td
(susceptibility,)Tj
5.6636 0 Td
(much)Tj
2.5228 0 Td
(less)Tj
1.6101 0 Td
(is)Tj
0.8447 0 Td
(known)Tj
3.0047 0 Td
(about)Tj
2.4945 0 Td
(the)Tj
1.474 0 Td
(types)Tj
2.2733 0 Td
(of)Tj
1.0148 0 Td
(regulatory)Tj
4.32 0 Td
(networks)Tj
3.9061 0 Td
(of)Tj
1.0148 0 Td
(expressed)Tj
-33.1594 -1.2983 Td
(genes)Tj
2.4377 0 Td
(that)Tj
1.7802 0 Td
(define)Tj
2.6985 0 Td
(the)Tj
1.4684 0 Td
(molecular)Tj
4.2236 0 Td
(signature)Tj
3.9118 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(disease.)Tj
3.2428 0 Td
(Besides)Tj
3.1634 0 Td
(important)Tj
4.2803 0 Td
(mRNA)Tj
3.0841 0 Td
(expression)Tj
-32.7796 -1.3039 Td
(alterations,)Tj
4.6317 0 Td
(Ps)Tj
1.1396 0 Td
(is)Tj
0.8503 0 Td
(also)Tj
1.7688 0 Td
(characterized)Tj
5.5559 0 Td
(by)Tj
1.1849 0 Td
(a)Tj
0.652 0 Td
(specific)Tj
3.1917 0 Td
(microRNA)Tj
4.6488 0 Td
(expression)Tj
4.4674 0 Td
(profile,)Tj
3.0671 0 Td
(distinct)Tj
3.2088 0 Td
(from)Tj
-34.367 -1.2982 Td
(that)Tj
1.7744 0 Td
(of)Tj
1.0148 0 Td
(healthy)Tj
3.1351 0 Td
(skin)Tj
1.8936 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(].)Tj
1.5987 0 Td
(In)Tj
1.1112 0 Td
(addition,)Tj
3.821 0 Td
(the)Tj
1.4684 0 Td
(meta-analysis)Tj
5.6522 0 Td
(produced)Tj
4.0479 0 Td
(a)Tj
0.6519 0 Td
(reference)Tj
3.9175 0 Td
(list)Tj
1.3946 0 Td
(of)Tj
1.0148 0 Td
(consistent)Tj
-32.4961 -1.2983 Td
(candidate)Tj
4.1045 0 Td
(genes)Tj
2.4378 0 Td
(for)Tj
1.3889 0 Td
(further)Tj
3.0274 0 Td
(investigation)Tj
5.3631 0 Td
(of)Tj
1.0148 0 Td
(psoriasis)Tj
3.6624 0 Td
(pathology)Tj
4.1782 0 Td
(and)Tj
1.7291 0 Td
(new)Tj
1.8766 0 Td
(therapeutic)Tj
4.7338 0 Td
(target)Tj
-33.5166 -1.3039 Td
(selection)Tj
3.719 0 Td
(with)Tj
1.9956 0 Td
(the)Tj
1.4683 0 Td
(use)Tj
1.5307 0 Td
(of)Tj
1.0205 0 Td
(genetic)Tj
3.067 0 Td
(markers)Tj
3.498 0 Td
([)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(].)Tj
-15.1029 -1.2983 Td
(Genistein)Tj
4.0762 0 Td
(\(4,5,7-trihydroxyisoflavone\))Tj
11.4122 0 Td
(is)Tj
0.8447 0 Td
(a)Tj
0.652 0 Td
(naturally)Tj
3.7813 0 Td
(occurring)Tj
4.1273 0 Td
(plant)Tj
2.2677 0 Td
(compound)Tj
4.5977 0 Td
(that)Tj
1.7745 0 Td
(exhib-)Tj
-34.7298 -1.2983 Td
(its)Tj
1.1451 0 Td
(multidirectional)Tj
6.6954 0 Td
(biological)Tj
4.0876 0 Td
(action.)Tj
2.9253 0 Td
(It)Tj
0.8561 0 Td
(displays)Tj
3.3902 0 Td
(antioxidant,)Tj
5.0399 0 Td
(antiproliferative,)Tj
6.8655 0 Td
(proapoptotic,)Tj
-31.0051 -1.3039 Td
(antiangiogenic,)Tj
6.3438 0 Td
(as)Tj
1.0148 0 Td
(well)Tj
1.8199 0 Td
(as)Tj
1.0148 0 Td
(estrogenic)Tj
4.3086 0 Td
(and)Tj
1.7291 0 Td
(anti-estrogenic)Tj
6.2079 0 Td
(activity.)Tj
3.3448 0 Td
(Ito's)Tj
1.9389 0 Td
(group)Tj
2.6079 0 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(])Tj
1.3776 0 Td
(investigated)Tj
-31.7081 -1.2982 Td
(topical)Tj
2.9139 0 Td
(application)Tj
4.6772 0 Td
(of)Tj
1.0148 0 Td
(Glyteer)Tj
3.1521 0 Td
(\(GL,)Tj
2.0409 0 Td
(soybean\))Tj
3.7984 0 Td
(on)Tj
1.2756 0 Td
(a)Tj
0.652 0 Td
(psoriatic)Tj
3.668 0 Td
(model)Tj
2.7439 0 Td
(in)Tj
1.0318 0 Td
(mice.)Tj
2.3811 0 Td
(This)Tj
1.9842 0 Td
(isoflavone)Tj
4.2576 0 Td
(has)Tj
-35.5915 -1.2983 Td
(also)Tj
1.7688 0 Td
(attracted)Tj
3.7247 0 Td
(attention)Tj
3.8437 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.6576 0 Td
(potent)Tj
2.812 0 Td
(agent)Tj
2.3868 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(treatment)Tj
4.1385 0 Td
(of)Tj
1.0148 0 Td
(Ps)Tj
1.1395 0 Td
([)Tj
0.83 0.64 0.02 0 k
(9)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(10)Tj
0 g
(])Tj
1.5137 0 Td
(not)Tj
1.5761 0 Td
(only)Tj
1.9729 0 Td
(due)Tj
1.7007 0 Td
(to)Tj
1.0262 0 Td
(its)Tj
1.1452 0 Td
(anti-)Tj
-35.2004 -1.3039 Td
(proliferative)Tj
5.0853 0 Td
(and)Tj
1.7348 0 Td
(immunosuppressive)Tj
8.2941 0 Td
(properties)Tj
4.2746 0 Td
(but)Tj
1.5534 0 Td
(also)Tj
1.7688 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.6576 0 Td
(mediator)Tj
3.8665 0 Td
(modulating)Tj
4.8585 0 Td
(expression)Tj
-33.1084 -1.2983 Td
(of)Tj
1.0147 0 Td
(various)Tj
3.1408 0 Td
(genes)Tj
2.4435 0 Td
(whose)Tj
2.7212 0 Td
(products)Tj
3.7531 0 Td
(are)Tj
1.4513 0 Td
(involved)Tj
3.651 0 Td
(among)Tj
2.9934 0 Td
(others)Tj
2.7099 0 Td
(in)Tj
1.0318 0 Td
(different)Tj
3.6566 0 Td
(phases)Tj
2.846 0 Td
(of)Tj
1.0148 0 Td
(inflamma-)Tj
-32.4281 -1.2982 Td
(tion)Tj
1.8425 0 Td
(and)Tj
1.7291 0 Td
(proliferation)Tj
5.2667 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(].)Tj
2.075 0 Td
(However,)Tj
4.0762 0 Td
(the)Tj
1.4683 0 Td
(explicit)Tj
3.1294 0 Td
(mechanism)Tj
4.8472 0 Td
(of)Tj
1.0148 0 Td
(genistein's)Tj
4.3994 0 Td
(action,)Tj
2.9196 0 Td
(especially)Tj
-32.7682 -1.2983 Td
(in)Tj
1.0318 0 Td
(human)Tj
3.0784 0 Td
(epithelial)Tj
3.8721 0 Td
(cells,)Tj
2.1486 0 Td
(is)Tj
0.8447 0 Td
(still)Tj
1.6384 0 Td
(not)Tj
1.5761 0 Td
(elucidated.)Tj
4.5467 0 Td
(Thus,)Tj
2.4718 0 Td
(we)Tj
1.3266 0 Td
(examined)Tj
4.1273 0 Td
(the)Tj
1.474 0 Td
(effects)Tj
2.7212 0 Td
(of)Tj
1.0148 0 Td
(genistein)Tj
3.8268 0 Td
(on)Tj
-35.6993 -1.3039 Td
(activated)Tj
3.7813 0 Td
(spontaneously)Tj
5.9528 0 Td
(immortalized)Tj
5.6125 0 Td
(human)Tj
3.0784 0 Td
(keratinocytes,)Tj
5.7543 0 Td
(psoriasis-like)Tj
6.2362 0 Td
(HaCaT)Tj
3.1294 0 Td
(cell)Tj
1.5591 0 Td
(line,)Tj
-35.104 -1.2983 Td
(to)Tj
1.0261 0 Td
(find)Tj
1.8482 0 Td
(new)Tj
1.8765 0 Td
(potential)Tj
3.7587 0 Td
(targets)Tj
2.8743 0 Td
(for)Tj
1.3833 0 Td
(therapy)Tj
3.2485 0 Td
(and/or)Tj
2.9367 0 Td
(to)Tj
1.0261 0 Td
(develop)Tj
3.3222 0 Td
(a)Tj
0.652 0 Td
(tool)Tj
1.7801 0 Td
(for)Tj
1.3833 0 Td
(treatment.)Tj
4.3653 0 Td
(Despite)Tj
3.2428 0 Td
(being)Tj
-34.7241 -1.2983 Td
(limited)Tj
3.0613 0 Td
(by)Tj
1.1736 0 Td
(the)Tj
1.4627 0 Td
(lack)Tj
1.8141 0 Td
(of)Tj
1.0091 0 Td
(many)Tj
2.4662 0 Td
(of)Tj
1.0091 0 Td
(the)Tj
1.4627 0 Td
(cellular)Tj
3.1294 0 Td
(players)Tj
3.0217 0 Td
(in)Tj
1.0261 0 Td
(psoriasis,)Tj
3.8891 0 Td
(including)Tj
4.0309 0 Td
(fibroblasts)Tj
4.3596 0 Td
(and)Tj
1.7235 0 Td
(inflam-)Tj
-34.6391 -1.3039 Td
(matory)Tj
3.101 0 Td
(cells,)Tj
2.1487 0 Td
(our)Tj
1.6271 0 Td
(monolayer)Tj
/F12 1 Tf
4.5297 0 Td
[()12()]TJ
1.0148 0 Td
[()-13()14()7()20()]TJ
/F8 1 Tf
2.0466 0 Td
(model)Tj
2.7439 0 Td
(of)Tj
1.0148 0 Td
(psoriasis-like)Tj
6.2362 0 Td
(HaCaT)Tj
3.1294 0 Td
(has)Tj
1.5421 0 Td
(proved)Tj
3.0217 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(a)Tj
0.6519 0 Td
(valu-)Tj
-34.9849 -1.2982 Td
(able)Tj
1.8311 0 Td
(first)Tj
1.8028 0 Td
(step)Tj
1.8199 0 Td
(model)Tj
2.7439 0 Td
(system)Tj
2.9423 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.4684 0 Td
(evaluation)Tj
4.3653 0 Td
(of)Tj
1.0148 0 Td
(nutraceutical)Tj
5.4425 0 Td
(agents)Tj
2.7496 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(genistein)Tj
3.8268 0 Td
(for)Tj
1.3833 0 Td
(Ps)Tj
-35.4952 -1.2983 Td
(improvement)Tj
5.6692 0 Td
([)Tj
0.83 0.64 0.02 0 k
(12)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(].)Tj
3.5433 0 Td
(Our)Tj
1.8708 0 Td
(results)Tj
2.8063 0 Td
(suggest)Tj
3.1238 0 Td
(that)Tj
1.7745 0 Td
(the)Tj
1.474 0 Td
(aberrant)Tj
3.6056 0 Td
(expression)Tj
4.4674 0 Td
(of)Tj
1.0148 0 Td
(genes)Tj
2.4378 0 Td
(contributing)Tj
-31.7875 -1.3039 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4683 0 Td
(progression)Tj
4.9209 0 Td
(of)Tj
1.0148 0 Td
(Ps)Tj
1.1396 0 Td
(can)Tj
1.627 0 Td
(be)Tj
1.1509 0 Td
(improved)Tj
4.1045 0 Td
(by)Tj
1.1849 0 Td
(the)Tj
1.4683 0 Td
(action)Tj
2.6986 0 Td
(of)Tj
1.0148 0 Td
(genistein;)Tj
4.0479 0 Td
(they)Tj
1.9218 0 Td
(also)Tj
1.7688 0 Td
(explain)Tj
3.1238 0 Td
(in)Tj
1.0375 0 Td
(detail)Tj
-34.7185 -1.2983 Td
(the)Tj
1.4683 0 Td
(effects)Tj
2.7269 0 Td
(of)Tj
1.0148 0 Td
(this)Tj
1.6724 0 Td
(isoflavone)Tj
4.2576 0 Td
(on)Tj
1.2756 0 Td
(signaling)Tj
3.8211 0 Td
(cascades)Tj
3.6113 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(human)Tj
3.0728 0 Td
(epithelial)Tj
3.8721 0 Td
(cell)Tj
1.559 0 Td
(line)Tj
1.7065 0 Td
(HaCaT.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 356.2015 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Materials)Tj
4.5071 0 Td
(and)Tj
1.989 0 Td
(methods)Tj
/F13 1 Tf
-6.4961 -1.5023 Td
(Cell)Tj
1.8803 0 Td
(lines,)Tj
2.4094 0 Td
(culture)Tj
3.1938 0 Td
(media)Tj
2.7921 0 Td
(and)Tj
1.7906 0 Td
(reagents)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 321.222 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Spontaneously)Tj
6.0661 0 Td
(immortalized)Tj
5.6182 0 Td
(human)Tj
3.0784 0 Td
(keratinocytes)Tj
5.5275 0 Td
(\(HaCaT)Tj
3.4696 0 Td
(cell)Tj
1.559 0 Td
(line\))Tj
2.0466 0 Td
(were)Tj
2.1203 0 Td
(purchased)Tj
4.3314 0 Td
(from)Tj
2.2053 0 Td
(the)Tj
-36.0224 -1.3039 Td
(CLS)Tj
1.8935 0 Td
(Cell)Tj
1.8028 0 Td
(Lines)Tj
2.3584 0 Td
(Service)Tj
3.0557 0 Td
(GmbH)Tj
3.0331 0 Td
(\(Eppelheim,)Tj
5.0967 0 Td
(Germany\))Tj
4.3256 0 Td
([)Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
(].)Tj
2.0806 0 Td
(HaCaT)Tj
3.1294 0 Td
(cells)Tj
1.9163 0 Td
(from)Tj
2.2053 0 Td
(passages)Tj
3.5773 0 Td
(3550)Tj
-34.4747 -1.2982 Td
(were)Tj
2.1203 0 Td
(maintained)Tj
4.7905 0 Td
(in)Tj
1.0318 0 Td
(Roswell)Tj
3.3108 0 Td
(Park)Tj
2.0806 0 Td
(Memorial)Tj
4.1839 0 Td
(Institute)Tj
3.583 0 Td
(1640)Tj
2.1203 0 Td
(medium)Tj
3.6057 0 Td
(\(RPMI)Tj
2.9763 0 Td
(1640,)Tj
2.3471 0 Td
(Gibco,)Tj
-32.1503 -1.2983 Td
(Thermo)Tj
3.4809 0 Td
(Fisher)Tj
2.6985 0 Td
(Scientific,)Tj
4.1273 0 Td
(Bleiswijk,)Tj
4.0251 0 Td
(Netherlands\))Tj
5.4595 0 Td
(supplemented)Tj
5.8564 0 Td
(with)Tj
1.9955 0 Td
(10%)Tj
1.9276 0 Td
(fetal)Tj
1.9105 0 Td
(bovine)Tj
2.9254 0 Td
(serum)Tj
-34.4067 -1.3039 Td
(\(FBS,)Tj
2.3697 0 Td
(Gibco,)Tj
2.863 0 Td
(Thermo)Tj
3.4809 0 Td
(Fisher)Tj
2.6986 0 Td
(Scientific,)Tj
4.1272 0 Td
(Bleiswijk,)Tj
4.0252 0 Td
(Netherlands\))Tj
5.4594 0 Td
(and)Tj
1.7292 0 Td
(1%)Tj
1.457 0 Td
(antibiotic/antimycotic)Tj
-28.2102 -1.2983 Td
(solution)Tj
3.4809 0 Td
(\(Gibco,)Tj
3.2031 0 Td
(Thermo)Tj
3.4809 0 Td
(Fisher)Tj
2.6986 0 Td
(Scientific,)Tj
4.1272 0 Td
(Bleiswijk,)Tj
4.0308 0 Td
(Netherlands\))Tj
5.4595 0 Td
(at)Tj
0.9525 0 Td
(37C)Tj
2.2223 0 Td
(in)Tj
1.0375 0 Td
(a)Tj
0.652 0 Td
(humidified)Tj
-31.3453 -1.2982 Td
(atmosphere)Tj
4.9039 0 Td
(containing)Tj
4.524 0 Td
(5%)Tj
1.457 0 Td
(carbon)Tj
3.0104 0 Td
(dioxide)Tj
3.2031 0 Td
(\(CO)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 388.5165 241.5118 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(2)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 392.0881 243.2125 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\).)Tj
0.7823 0 Td
(THP-1)Tj
2.982 0 Td
(cells)Tj
1.9219 0 Td
(\(CLS)Tj
2.2394 0 Td
(Cell)Tj
1.7971 0 Td
(Lines)Tj
2.3584 0 Td
(Service)Tj
3.0614 0 Td
(GmbH\))Tj
-34.3499 -1.3039 Td
(were)Tj
2.1203 0 Td
(routinely)Tj
3.8664 0 Td
(maintained)Tj
4.7849 0 Td
(in)Tj
1.0375 0 Td
(RPMI)Tj
2.6362 0 Td
(1640)Tj
2.1203 0 Td
(medium)Tj
3.6055 0 Td
(supplemented)Tj
5.8564 0 Td
(with)Tj
1.9955 0 Td
(2)Tj
0.6974 0 Td
(mM)Tj
1.9332 0 Td
(glutamine)Tj
-30.6536 -1.2982 Td
(\(Gibco,)Tj
3.2031 0 Td
(Thermo)Tj
3.4753 0 Td
(Fisher)Tj
2.6986 0 Td
(Scientific,)Tj
4.1215 0 Td
(Bleiswijk,)Tj
4.0252 0 Td
(Netherlands\))Tj
5.4594 0 Td
(and)Tj
1.7234 0 Td
(10%)Tj
1.9276 0 Td
(FBS)Tj
1.8028 0 Td
(\(Gibco,)Tj
3.2031 0 Td
(Thermo)Tj
3.4753 0 Td
(Fisher)Tj
-35.1153 -1.2983 Td
(Scientific,)Tj
4.1272 0 Td
(Bleiswijk,)Tj
4.0252 0 Td
(Netherlands\))Tj
5.4595 0 Td
(at)Tj
0.9524 0 Td
(28)Tj
1.6895 0 Td
(x)Tj
0.6859 0 Td
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 378.8787 208.6299 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(5)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 384.6614 204.2078 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(cells/mL.)Tj
3.8324 0 Td
(Genistein)Tj
4.0762 0 Td
(was)Tj
1.6951 0 Td
(synthetized)Tj
4.7678 0 Td
(at)Tj
0.9524 0 Td
(the)Tj
1.4684 0 Td
(Phar-)Tj
-35.257 -1.2982 Td
(maceutical)Tj
4.5184 0 Td
(Research)Tj
3.8041 0 Td
(Institute)Tj
3.5829 0 Td
(\(Warsaw,)Tj
4.0365 0 Td
(Poland\).)Tj
3.6056 0 Td
(The)Tj
1.7858 0 Td
(flavonoid)Tj
3.9968 0 Td
(was)Tj
1.7008 0 Td
(dissolved)Tj
3.8948 0 Td
(in)Tj
1.0374 0 Td
(dimethyl)Tj
3.7814 0 Td
(sulf-)Tj
-35.7445 -1.3039 Td
(oxide)Tj
2.4094 0 Td
(\(DMSO,)Tj
3.634 0 Td
(Sigma-Aldrich,)Tj
6.3099 0 Td
(St.)Tj
1.2189 0 Td
(Louis,)Tj
2.6419 0 Td
(USA\))Tj
2.4603 0 Td
(and)Tj
1.7291 0 Td
(added)Tj
2.6589 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(indicated)Tj
3.9402 0 Td
(final)Tj
2.0012 0 Td
(concentrations)Tj
-31.5096 -1.2983 Td
(as)Tj
1.0148 0 Td
(determined)Tj
4.8472 0 Td
(in)Tj
1.0375 0 Td
(previous)Tj
3.651 0 Td
(studies)Tj
2.9877 0 Td
([)Tj
0.83 0.64 0.02 0 k
(18)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(19)Tj
0 g
(])Tj
1.5137 0 Td
(to)Tj
1.0204 0 Td
(cell)Tj
1.559 0 Td
(cultures.)Tj
3.6283 0 Td
(Methotrexate)Tj
5.5842 0 Td
(\(MTX\))Tj
3.0557 0 Td
(was)Tj
1.7008 0 Td
(purchased)Tj
-33.3351 -1.2983 Td
(from)Tj
2.2053 0 Td
(Sigma-Aldrich)Tj
6.0775 0 Td
(\(St.)Tj
1.559 0 Td
(Louis,)Tj
2.6476 0 Td
(USA\).)Tj
2.6815 0 Td
(It)Tj
0.8617 0 Td
(was)Tj
1.6951 0 Td
(dissolved)Tj
3.8947 0 Td
(in)Tj
1.0375 0 Td
(DMSO)Tj
3.0727 0 Td
(and)Tj
1.7292 0 Td
(added)Tj
2.6588 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4684 0 Td
(indicated)Tj
-32.6265 -1.3039 Td
(final)Tj
2.0012 0 Td
(concentrations)Tj
6.1795 0 Td
([)Tj
0.83 0.64 0.02 0 k
(20)Tj
0 g
(].)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 112.9889 cm
BT
/F13 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Cell-viability)Tj
5.6268 0 Td
(assays)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 95.9811 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Cell)Tj
1.7971 0 Td
(viability)Tj
3.4186 0 Td
(was)Tj
1.6951 0 Td
(evaluated)Tj
3.9911 0 Td
(by)Tj
1.1849 0 Td
(MTT)Tj
2.3301 0 Td
(\(3-\(4,5-dimethylthia)Tj
8.1297 0 Td
(zol-2-yl\)-2,5-diphenyltetrazolium)Tj
-22.5466 -1.2982 Td
(bromide\))Tj
3.9798 0 Td
(assay.)Tj
2.4944 0 Td
(For)Tj
1.6214 0 Td
(cell)Tj
1.5591 0 Td
(cytotoxic)Tj
3.8664 0 Td
(assay)Tj
2.2677 0 Td
(and)Tj
1.7291 0 Td
(proliferation)Tj
5.2668 0 Td
(assay,)Tj
2.4888 0 Td
(1.25)Tj
1.8708 0 Td
(x)Tj
0.686 0 Td
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 487.8425 87.4204 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(4)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 493.5685 82.9984 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(or)Tj
1.0998 0 Td
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 514.0913 87.4204 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(3)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 519.8173 82.9984 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(HaCaT)Tj
3.1294 0 Td
(cells,)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 399.7984 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Isoflavone)Tj
4.6984 0 Td
(genistein)Tj
4.1386 0 Td
(in)Tj
0.978 0 Td
(the)Tj
1.5874 0 Td
(epithelial)Tj
4.0748 0 Td
(cell)Tj
1.6867 0 Td
(line)Tj
1.7362 0 Td
(HaCaT)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01922)Tj
4.089 0 Td
(97)Tj
0 g
2.0906 0 Td
(February)Tj
4.1599 0 Td
(14,)Tj
1.5874 0 Td
(2018)Tj
33.1585 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(27)Tj
ET
Q
q
0.83 0.64 0.02 0 k
1 j
1 J
0 w
36 707.6409 m
97.6819 707.6409 l
h
f*
7.9999 0 0 7.9999 36 708.7181 cm
BT
/F10 1 Tf
1 TL
-0.025 Tc
0 0 Td
(www.ncb)Tj
3.5079 0 Td
(r.gov.pl/en/)Tj
0 g
(.)Tj
4.6417 0 Td
(The)Tj
1.5874 0 Td
(funders)Tj
3.0473 0 Td
(had)Tj
1.5874 0 Td
(a)Tj
0.6449 0 Td
(role)Tj
1.6158 0 Td
(in)Tj
0.8858 0 Td
(the)Tj
-17.5182 -1.3748 Td
(study)Tj
2.2677 0 Td
(design,)Tj
2.8984 0 Td
(data)Tj
1.793 0 Td
(collection)Tj
3.7346 0 Td
(and)Tj
1.5874 0 Td
(analysis.)Tj
/F9 1 Tf
-12.2811 -2.126 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F10 1 Tf
0.4819 0 Td
(The)Tj
1.5875 0 Td
(authors)Tj
3.0401 0 Td
(have)Tj
1.963 0 Td
(declared)Tj
-14.7827 -1.3748 Td
(that)Tj
1.6228 0 Td
(no)Tj
1.1693 0 Td
(competing)Tj
4.1599 0 Td
(interests)Tj
ET
endstream
endobj
35 0 obj
<>stream
endstream
endobj
36 0 obj
<>stream
endstream
endobj
37 0 obj
<>stream
endstream
endobj
38 0 obj
<>stream
endstream
endobj
39 0 obj
<>stream
endstream
endobj
40 0 obj
<>stream
endstream
endobj
41 0 obj
<>stream
endstream
endobj
42 0 obj
<>stream
endstream
endobj
43 0 obj
<>stream
endstream
endobj
44 0 obj
<>stream
endstream
endobj
45 0 obj
<>stream
endstream
endobj
46 0 obj
<>stream
endstream
endobj
47 0 obj
<>stream
endstream
endobj
48 0 obj
<>stream
endstream
endobj
49 0 obj
<>stream
endstream
endobj
50 0 obj
<>stream
endstream
endobj
51 0 obj
<>stream
BT
10.3394 -4.8756 Td
(exist.)Tj
ET
Q
endstream
endobj
52 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 13 0 R/Annots 55 0 R/Contents 56 0 R/TrimBox[0 0 612 792]>>
endobj
55 0 obj
[57 0 R 58 0 R]
endobj
57 0 obj
<>/Border[0 0 0]/Dest(Rpone.0192297.ref021)>>
endobj
58 0 obj
<>/Border[0 0 0]/A 59 0 R>>
endobj
59 0 obj
<>
endobj
56 0 obj
[60 0 R 61 0 R 62 0 R 63 0 R]
endobj
60 0 obj
<>stream
q
0.83 0.64 0.02 0 k
228.5291 362.0976 m
238.0535 362.0976 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(respectively,)Tj
5.1079 0 Td
(were)Tj
2.126 0 Td
(seeded)Tj
2.9027 0 Td
(per)Tj
1.5363 0 Td
(well)Tj
1.8199 0 Td
(in)Tj
1.0318 0 Td
(96-well)Tj
3.1237 0 Td
(culture)Tj
3.0388 0 Td
(plates)Tj
2.5001 0 Td
(and)Tj
1.7291 0 Td
(incubated)Tj
4.1783 0 Td
(overnight.)Tj
4.3086 0 Td
(Growth)Tj
-33.4032 -1.3039 Td
(medium)Tj
3.6056 0 Td
(was)Tj
1.6951 0 Td
(then)Tj
2.0183 0 Td
(substituted)Tj
4.6204 0 Td
(with)Tj
1.9956 0 Td
(fresh)Tj
2.194 0 Td
(medium)Tj
3.6056 0 Td
(supplemented)Tj
5.8507 0 Td
(with)Tj
2.0012 0 Td
(tested)Tj
2.5512 0 Td
(compounds)Tj
4.9606 0 Td
(at)Tj
-35.0983 -1.2982 Td
(appropriate)Tj
4.8755 0 Td
(concentrations)Tj
6.1795 0 Td
(or)Tj
1.0998 0 Td
(0.05%)Tj
2.6306 0 Td
(DMSO)Tj
3.0727 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(control)Tj
3.1237 0 Td
(\(in)Tj
1.372 0 Td
(cultures)Tj
3.4015 0 Td
(with)Tj
1.9956 0 Td
(tested)Tj
2.5512 0 Td
(compounds,)Tj
-31.9689 -1.2983 Td
(DMSO)Tj
3.0727 0 Td
(final)Tj
2.0012 0 Td
(concentration)Tj
5.8167 0 Td
(was)Tj
1.7008 0 Td
(also)Tj
1.7688 0 Td
(adjusted)Tj
3.5773 0 Td
(to)Tj
1.0261 0 Td
(0.05%\).)Tj
3.1918 0 Td
(Following)Tj
4.2179 0 Td
(incubation)Tj
4.5524 0 Td
(for)Tj
1.3833 0 Td
(24)Tj
1.1736 0 Td
(and)Tj
1.7291 0 Td
(48)Tj
-35.2117 -1.2983 Td
(hours)Tj
2.5114 0 Td
(\(to)Tj
1.3663 0 Td
(test)Tj
1.6044 0 Td
(cytotoxicity\))Tj
5.2214 0 Td
(or)Tj
1.0998 0 Td
(for)Tj
1.3833 0 Td
(7)Tj
0.6974 0 Td
(-days)Tj
2.347 0 Td
(\(to)Tj
1.3663 0 Td
(test)Tj
1.6044 0 Td
(cell)Tj
1.5591 0 Td
(proliferation\),)Tj
5.828 0 Td
(medium)Tj
3.6056 0 Td
(was)Tj
1.7008 0 Td
(substituted)Tj
-31.8952 -1.3039 Td
(with)Tj
1.9955 0 Td
(MTT)Tj
2.3358 0 Td
(solution)Tj
3.4809 0 Td
(\(1)Tj
1.0375 0 Td
(mg/mL)Tj
3.1917 0 Td
(in)Tj
1.0375 0 Td
(RPMI)Tj
2.6306 0 Td
(1640)Tj
2.1259 0 Td
(medium,)Tj
3.8268 0 Td
(Sigma-Aldrich,)Tj
6.3099 0 Td
(St.)Tj
1.2188 0 Td
(Louis,)Tj
2.6419 0 Td
(USA\);)Tj
2.6816 0 Td
(and)Tj
-34.5144 -1.2982 Td
(after)Tj
2.0352 0 Td
(a)Tj
0.652 0 Td
(2-hour)Tj
2.982 0 Td
(incubation)Tj
4.5467 0 Td
(at)Tj
0.9525 0 Td
(37C)Tj
2.228 0 Td
(the)Tj
1.4683 0 Td
(formazan)Tj
4.0365 0 Td
(product)Tj
3.3903 0 Td
(was)Tj
1.7007 0 Td
(dissolved)Tj
3.8948 0 Td
(in)Tj
1.0375 0 Td
(DMSO)Tj
3.0727 0 Td
(and)Tj
1.7292 0 Td
(absor-)Tj
-33.7264 -1.2983 Td
(bance)Tj
2.5568 0 Td
(was)Tj
1.6951 0 Td
(read)Tj
1.9786 0 Td
(at)Tj
0.9524 0 Td
(550)Tj
1.6441 0 Td
(nm)Tj
1.593 0 Td
(\(VICTOR)Tj
4.235 0 Td
(Multilabel)Tj
4.3086 0 Td
(Plate)Tj
2.1827 0 Td
(Reader,)Tj
3.2485 0 Td
(PerkinElmer\).)Tj
5.879 0 Td
(The)Tj
1.7801 0 Td
(optical)Tj
2.914 0 Td
(den-)Tj
-34.9679 -1.3039 Td
(sity)Tj
1.5987 0 Td
(of)Tj
1.0148 0 Td
(formazan)Tj
4.0365 0 Td
(formed)Tj
3.1578 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(control)Tj
3.1181 0 Td
(was)Tj
1.7007 0 Td
(taken)Tj
2.4208 0 Td
(as)Tj
1.0148 0 Td
(100%)Tj
2.4038 0 Td
(of)Tj
1.0148 0 Td
(cell)Tj
1.559 0 Td
(viability.)Tj
3.6453 0 Td
(Samples)Tj
3.498 0 Td
(were)Tj
-32.6889 -1.2983 Td
(measured)Tj
4.1045 0 Td
(in)Tj
1.0375 0 Td
(quintuplicate,)Tj
5.7316 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.474 0 Td
(experiment)Tj
4.7735 0 Td
(was)Tj
1.7008 0 Td
(repeated)Tj
3.6397 0 Td
(three)Tj
2.262 0 Td
(times.)Tj
2.6192 0 Td
(LC)Tj
1.4173 0 Td
(\(cytotoxicity)Tj
-30.4892 -1.2983 Td
(assay\))Tj
2.6021 0 Td
(and)Tj
1.7292 0 Td
(IC)Tj
1.2245 0 Td
(\(proliferation)Tj
5.6069 0 Td
(assay\))Tj
2.6079 0 Td
(index)Tj
2.4491 0 Td
(values)Tj
2.6702 0 Td
(of)Tj
1.0148 0 Td
(genistein)Tj
3.8211 0 Td
(was)Tj
1.7008 0 Td
(determined)Tj
4.8472 0 Td
(for)Tj
1.3889 0 Td
(each)Tj
2.0296 0 Td
(com-)Tj
-33.6923 -1.3039 Td
(pound)Tj
2.8459 0 Td
(in)Tj
1.0375 0 Td
(comparison)Tj
4.9776 0 Td
(to)Tj
1.0205 0 Td
(non-treated)Tj
4.9549 0 Td
(cultures)Tj
3.3959 0 Td
(\(incubated)Tj
4.5184 0 Td
(with)Tj
2.0012 0 Td
(DMSO)Tj
3.0671 0 Td
(only\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 536.2015 cm
BT
/F13 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Two-dimensional)Tj
7.5591 0 Td
(\(2D\))Tj
2.1732 0 Td
(engineered)Tj
4.7953 0 Td
(skin)Tj
1.9559 0 Td
(psoriatic)Tj
3.8741 0 Td
(cells)Tj
2.0173 0 Td
(model)Tj
2.8347 0 Td
(development)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 211.9748 519.1937 cm
BT
/F13 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Direct)Tj
2.8686 0 Td
(psoriatic)Tj
3.8721 0 Td
(stimulation.)Tj
/F8 1 Tf
5.896 0 Td
(HaCaT)Tj
3.1294 0 Td
(cells)Tj
1.9163 0 Td
(were)Tj
2.1259 0 Td
(cultured)Tj
3.566 0 Td
(to)Tj
1.0261 0 Td
(80%)Tj
1.9276 0 Td
(of)Tj
1.0148 0 Td
(confluence)Tj
4.5807 0 Td
(in)Tj
1.0318 0 Td
(flasks)Tj
-34.1515 -1.2982 Td
(containing)Tj
4.524 0 Td
(RPMI)Tj
2.6362 0 Td
(medium)Tj
3.6057 0 Td
(supplemented)Tj
5.8563 0 Td
(with)Tj
1.9956 0 Td
(10%)Tj
1.9275 0 Td
(FBS)Tj
1.8028 0 Td
(and)Tj
1.7292 0 Td
(1%)Tj
1.457 0 Td
(antibiotic/antimycotic)Tj
9.1048 0 Td
(solu-)Tj
-34.6391 -1.3039 Td
(tion)Tj
1.8424 0 Td
(and)Tj
1.7292 0 Td
(then)Tj
2.0182 0 Td
(the)Tj
1.4684 0 Td
(cells)Tj
1.9218 0 Td
(were)Tj
2.1203 0 Td
(disaggregated)Tj
5.6863 0 Td
(using)Tj
2.3868 0 Td
(0.025%)Tj
3.1067 0 Td
(trypsin)Tj
3.0387 0 Td
(with)Tj
1.9956 0 Td
(0.01%)Tj
2.6305 0 Td
(EDTA.)Tj
3.0444 0 Td
(Cells)Tj
2.16 0 Td
(were)Tj
-35.1493 -1.2983 Td
(seeded)Tj
2.9083 0 Td
(at)Tj
0.9524 0 Td
(a)Tj
0.652 0 Td
(density)Tj
3.101 0 Td
(of)Tj
1.0148 0 Td
(4)Tj
0.6974 0 Td
(x)Tj
0.6803 0 Td
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 309.6 484.6677 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(5)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 315.3826 480.1889 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(cells/well)Tj
3.8494 0 Td
(in)Tj
1.0374 0 Td
(6-well)Tj
2.6419 0 Td
(plates)Tj
2.5002 0 Td
(in)Tj
1.0374 0 Td
(defined)Tj
3.2258 0 Td
(serum-free)Tj
4.5808 0 Td
(defined)Tj
3.2258 0 Td
(keratino-)Tj
-33.6356 -1.2982 Td
(cyte)Tj
1.8198 0 Td
(medium)Tj
3.6057 0 Td
(\(Keratinocyte-SFM,)Tj
8.1523 0 Td
(Gibco,)Tj
2.8686 0 Td
(Thermo)Tj
3.4809 0 Td
(Fisher)Tj
2.6986 0 Td
(Scientific,)Tj
4.1272 0 Td
(CA,)Tj
1.7915 0 Td
(USA\))Tj
2.4548 0 Td
(supplemented)Tj
-30.9994 -1.2983 Td
(with)Tj
1.9956 0 Td
(a)Tj
0.652 0 Td
(pituitary)Tj
3.6566 0 Td
(extract)Tj
2.9367 0 Td
(including)Tj
4.0421 0 Td
(insulin)Tj
2.9877 0 Td
(\(BPE\))Tj
2.6078 0 Td
(and)Tj
1.7292 0 Td
(epidermal)Tj
4.2519 0 Td
(growth)Tj
3.0727 0 Td
(factor)Tj
2.5399 0 Td
(\(EGF\))Tj
2.7155 0 Td
(\(Gibco,)Tj
-33.1877 -1.3039 Td
(Thermo)Tj
3.4809 0 Td
(Fisher)Tj
2.6986 0 Td
(Scientific,)Tj
4.1272 0 Td
(CA,)Tj
1.7914 0 Td
(USA\).)Tj
2.6816 0 Td
(After)Tj
2.2847 0 Td
(a)Tj
0.6519 0 Td
(24-hour)Tj
3.4583 0 Td
(incubation)Tj
4.5467 0 Td
(cells)Tj
1.9219 0 Td
(were)Tj
2.1203 0 Td
(cultivated)Tj
4.1216 0 Td
(in)Tj
-33.8851 -1.2983 Td
(serum-free)Tj
4.5808 0 Td
(keratinocyte)Tj
5.1647 0 Td
(medium)Tj
3.6055 0 Td
(without)Tj
3.3279 0 Td
(growth)Tj
3.0784 0 Td
(supplements)Tj
5.261 0 Td
(for)Tj
1.389 0 Td
(16)Tj
1.1679 0 Td
(hours.)Tj
2.7382 0 Td
(For)Tj
1.6271 0 Td
(further)Tj
3.0274 0 Td
(exper-)Tj
-34.9679 -1.2982 Td
(iments,)Tj
3.1635 0 Td
(cells)Tj
1.9218 0 Td
(were)Tj
2.1203 0 Td
(stimulated)Tj
4.422 0 Td
(with)Tj
2.0012 0 Td
(a)Tj
0.652 0 Td
(combination)Tj
5.3461 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.6519 0 Td
(proinflammator)Tj
6.4346 0 Td
(y)Tj
0.6747 0 Td
(cytokine)Tj
4.0308 0 Td
(mix:)Tj
2.3868 0 Td
(IL-1A,)Tj
-34.8205 -1.3039 Td
(IL-17A,)Tj
3.3109 0 Td
(IL-22,)Tj
2.6248 0 Td
(oncostatin)Tj
4.4107 0 Td
(M)Tj
1.1112 0 Td
(\(OSM\),)Tj
3.2427 0 Td
(and)Tj
1.7291 0 Td
(tumor)Tj
2.7439 0 Td
(necrosis)Tj
3.481 0 Td
(factor-)Tj
/F14 1 Tf
()Tj
/F8 1 Tf
3.4639 0 Td
(\(TNF-)Tj
/F14 1 Tf
()Tj
/F8 1 Tf
(\))Tj
3.6963 0 Td
(\(Gibco,)Tj
3.2032 0 Td
(Thermo)Tj
-33.0177 -1.2983 Td
(Fisher)Tj
2.6986 0 Td
(Scientific,)Tj
4.1272 0 Td
(CA,)Tj
1.7915 0 Td
(USA\))Tj
2.4548 0 Td
(2)Tj
0.6972 0 Td
(ng/mL)Tj
2.9197 0 Td
(each)Tj
2.0295 0 Td
(or)Tj
1.0999 0 Td
(lipopolysaccharide)Tj
7.6762 0 Td
(\(LPS,)Tj
2.3584 0 Td
(from)Tj
/F12 1 Tf
2.2053 0 Td
[()-4()-3( )13(\n)6()2()-9()4( )13(\n)18()4()]TJ
4.6261 0 Td
[( )7()10(\r)12()]TJ
-34.6844 -1.2983 Td
[()]TJ
/F8 1 Tf
(:)Tj
/F12 1 Tf
[()]TJ
/F8 1 Tf
(,)Tj
3.1011 0 Td
(Sigma-Aldrich,)Tj
6.3042 0 Td
(St.)Tj
1.2189 0 Td
(Louis,)Tj
2.6474 0 Td
(USA\))Tj
2.4548 0 Td
(1)Tj
/F15 1 Tf
0.6973 0 Td
[()]TJ
/F8 1 Tf
(g/mL)Tj
2.88 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(presence)Tj
3.7077 0 Td
(or)Tj
1.0999 0 Td
(absence)Tj
3.3392 0 Td
(of)Tj
1.0148 0 Td
(genistein)Tj
3.8267 0 Td
(for)Tj
1.3833 0 Td
(24)Tj
-36.1811 -1.3039 Td
(hours)Tj
2.5115 0 Td
([)Tj
0.83 0.64 0.02 0 k
(21)Tj
0 g
(].)Tj
2.0806 0 Td
(The)Tj
1.7802 0 Td
(control)Tj
3.1237 0 Td
(cells)Tj
1.9162 0 Td
(were)Tj
2.1259 0 Td
(left)Tj
1.474 0 Td
(untreated.)Tj
/F13 1 Tf
-13.8159 -1.2983 Td
(Indirect)Tj
3.5887 0 Td
(psoriatic)Tj
3.8777 0 Td
(stimulation.)Tj
/F8 1 Tf
5.8903 0 Td
(The)Tj
1.7801 0 Td
(Transwell)Tj
4.1499 0 Td
(cell)Tj
1.5591 0 Td
(culture)Tj
3.0387 0 Td
(system)Tj
2.9367 0 Td
(was)Tj
1.7008 0 Td
(used)Tj
2.0579 0 Td
(to)Tj
1.0261 0 Td
(co-culture)Tj
-32.8022 -1.2982 Td
(THP-1)Tj
2.982 0 Td
(with)Tj
1.9956 0 Td
(HaCaT.)Tj
3.3562 0 Td
(THP-1)Tj
2.9877 0 Td
(cells)Tj
1.9161 0 Td
(\(3)Tj
1.0375 0 Td
(x)Tj
0.686 0 Td
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 359.1496 341.6314 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(6)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 362.6645 337.2094 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\))Tj
0.5612 0 Td
(were)Tj
2.126 0 Td
(cultured)Tj
3.5659 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(upper)Tj
2.5739 0 Td
(compartment)Tj
5.6806 0 Td
(in)Tj
1.0375 0 Td
(cell)Tj
1.559 0 Td
(cul-)Tj
-35.8749 -1.2982 Td
(ture)Tj
1.8425 0 Td
(membrane)Tj
4.5637 0 Td
(inserts)Tj
2.8517 0 Td
(\(Corning)Tj
3.9287 0 Td
(#353102\),)Tj
4.1158 0 Td
(and)Tj
1.7291 0 Td
(HaCaT)Tj
3.1295 0 Td
(cells)Tj
1.9219 0 Td
(\(4)Tj
1.0374 0 Td
(x)Tj
0.686 0 Td
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 467.6031 328.6488 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(5)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 471.1181 324.2267 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\))Tj
0.5612 0 Td
(were)Tj
2.1203 0 Td
(cultured)Tj
3.5716 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
-34.3952 -1.3039 Td
(lower)Tj
2.4491 0 Td
(compartment)Tj
5.6806 0 Td
(in)Tj
1.0375 0 Td
(6-well)Tj
2.6475 0 Td
(plates,)Tj
2.7269 0 Td
(both)Tj
2.058 0 Td
(cell)Tj
1.559 0 Td
(lines)Tj
2.0693 0 Td
(in)Tj
1.0318 0 Td
(RPMI)Tj
2.6362 0 Td
(medium)Tj
3.6055 0 Td
(supplemented)Tj
5.8507 0 Td
(with)Tj
2.0012 0 Td
(10%)Tj
-35.3533 -1.2982 Td
(FBS)Tj
1.8028 0 Td
(and)Tj
1.7291 0 Td
(1%)Tj
1.4513 0 Td
(antibiotic/antimycoti)Tj
8.4699 0 Td
(c)Tj
0.6406 0 Td
(solution.)Tj
3.7077 0 Td
(For)Tj
1.6271 0 Td
(the)Tj
1.4683 0 Td
(co-cultivation)Tj
5.777 0 Td
(studies,)Tj
3.2087 0 Td
(HaCaT)Tj
3.1294 0 Td
(cells)Tj
1.9219 0 Td
(grown)Tj
-34.9338 -1.2983 Td
(in)Tj
1.0318 0 Td
(six-well)Tj
3.2655 0 Td
(plates)Tj
2.5001 0 Td
(were)Tj
2.126 0 Td
(washed)Tj
3.1748 0 Td
(twice)Tj
2.3187 0 Td
(with)Tj
1.9956 0 Td
(phosphate)Tj
4.3369 0 Td
(buffered)Tj
3.5717 0 Td
(saline)Tj
2.5001 0 Td
(\(PBS\).)Tj
2.7438 0 Td
(The)Tj
1.7802 0 Td
(cell)Tj
1.559 0 Td
(culture)Tj
-32.9042 -1.3039 Td
(insert)Tj
2.4888 0 Td
(was)Tj
1.7007 0 Td
(then)Tj
2.0183 0 Td
(placed)Tj
2.7893 0 Td
(on)Tj
1.2756 0 Td
(top)Tj
1.542 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(HaCaT)Tj
3.1351 0 Td
(cells)Tj
1.9162 0 Td
(to)Tj
1.0262 0 Td
(avoid)Tj
2.4094 0 Td
(physical)Tj
3.4526 0 Td
(contact)Tj
3.152 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(different)Tj
3.651 0 Td
(cell)Tj
-35.5291 -1.2983 Td
(lines)Tj
2.0636 0 Td
(\(indirect)Tj
3.6907 0 Td
(co-culture\).)Tj
4.8812 0 Td
(HaCaT)Tj
3.1294 0 Td
(and)Tj
1.7348 0 Td
(THP-1)Tj
2.982 0 Td
(cells)Tj
1.9219 0 Td
(were)Tj
2.1203 0 Td
(stimulated)Tj
4.422 0 Td
(with)Tj
2.0012 0 Td
(1)Tj
/F15 1 Tf
0.6916 0 Td
[()]TJ
/F8 1 Tf
(g/mL)Tj
2.88 0 Td
(LPS)Tj
1.7915 0 Td
(\(Sigma-)Tj
-34.3102 -1.2982 Td
(Aldrich,)Tj
3.4922 0 Td
(St.)Tj
1.2189 0 Td
(Louis,)Tj
2.6476 0 Td
(USA\))Tj
2.4548 0 Td
(for)Tj
1.3889 0 Td
(24)Tj
1.1679 0 Td
(hours)Tj
2.5171 0 Td
(of)Tj
1.0148 0 Td
(co-culturing)Tj
5.1761 0 Td
(with)Tj
1.9955 0 Td
(the)Tj
1.4684 0 Td
(Transwell)Tj
4.1498 0 Td
(cell)Tj
1.559 0 Td
(culture)Tj
3.0387 0 Td
(inserts.)Tj
-33.2897 -1.304 Td
(Additionally,)Tj
5.4538 0 Td
(3)Tj
0.6973 0 Td
(mL)Tj
1.5761 0 Td
(supplemented)Tj
5.8563 0 Td
(RPMI)Tj
2.6305 0 Td
(medium)Tj
3.6057 0 Td
(was)Tj
1.7008 0 Td
(added)Tj
2.6588 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(HaCaT)Tj
3.1293 0 Td
(monolayer)Tj
-29.8031 -1.2982 Td
(\(control\).)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 192.0188 cm
BT
/F13 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(DNA)Tj
2.4141 0 Td
(microarray)Tj
4.8898 0 Td
(processing)Tj
4.6442 0 Td
(and)Tj
1.7905 0 Td
(real-time)Tj
4.0394 0 Td
(quantitative)Tj
5.282 0 Td
(RT-PCR)Tj
3.7795 0 Td
(assays)Tj
2.7591 0 Td
(for)Tj
-29.5986 -1.1669 Td
(mRNA)Tj
3.1512 0 Td
(analysis)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 161.0078 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Total)Tj
2.313 0 Td
(RNA)Tj
2.262 0 Td
(was)Tj
1.7008 0 Td
(extracted)Tj
3.8835 0 Td
(from)Tj
2.211 0 Td
(cells)Tj
1.9162 0 Td
(using)Tj
2.3924 0 Td
(the)Tj
1.4683 0 Td
(High)Tj
2.2451 0 Td
(Pure)Tj
2.1033 0 Td
(RNA)Tj
2.262 0 Td
(Isolation)Tj
3.7304 0 Td
(Kit)Tj
1.457 0 Td
(\(Roche)Tj
3.067 0 Td
(Applied)Tj
-33.012 -1.2982 Td
(Science,)Tj
3.4298 0 Td
(Indianapolis,)Tj
5.4425 0 Td
(USA\))Tj
2.4548 0 Td
(following)Tj
3.9798 0 Td
(the)Tj
1.4684 0 Td
(manufacturer's)Tj
6.2645 0 Td
(instructions.)Tj
5.2271 0 Td
(The)Tj
1.7801 0 Td
(quality)Tj
2.9594 0 Td
(and)Tj
1.7291 0 Td
(quan-)Tj
-34.7355 -1.3039 Td
(tity)Tj
1.5363 0 Td
(of)Tj
1.0148 0 Td
(each)Tj
2.0296 0 Td
(RNA)Tj
2.262 0 Td
(sample)Tj
3.0218 0 Td
(was)Tj
1.7007 0 Td
(evaluated)Tj
3.9855 0 Td
(using)Tj
2.3924 0 Td
(the)Tj
1.4684 0 Td
(RNA)Tj
2.262 0 Td
(6000)Tj
2.126 0 Td
(Nano)Tj
2.4434 0 Td
(Assay)Tj
2.5115 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.474 0 Td
(Agilent)Tj
3.1521 0 Td
(2100)Tj
-34.6561 -1.2983 Td
(Bioanalyser)Tj
4.8472 0 Td
(\(Agilent)Tj
3.4922 0 Td
(Technologies)Tj
5.5332 0 Td
(Inc.,)Tj
1.9786 0 Td
(USA\).)Tj
2.6815 0 Td
(Next,)Tj
2.3698 0 Td
(total)Tj
2.0069 0 Td
(RNA)Tj
2.262 0 Td
(was)Tj
1.6952 0 Td
(retrotranscribed)Tj
6.7237 0 Td
(with)Tj
2.0012 0 Td
(the)Tj
-35.5915 -1.2983 Td
(Transcriptor)Tj
5.3007 0 Td
(First-Strand)Tj
5.0513 0 Td
(cDNA)Tj
2.8006 0 Td
(Synthesis)Tj
3.9402 0 Td
(Kit)Tj
1.457 0 Td
(\(Roche)Tj
3.0614 0 Td
(Applied)Tj
3.4072 0 Td
(Science,)Tj
3.4299 0 Td
(Indianapolis,)Tj
5.4425 0 Td
(USA\).)Tj
-33.8908 -1.3039 Td
(To)Tj
1.3379 0 Td
(identify)Tj
3.2938 0 Td
(genes)Tj
2.4435 0 Td
(regulated)Tj
3.9344 0 Td
(differentially)Tj
5.3065 0 Td
(by)Tj
1.1792 0 Td
(genistein,)Tj
4.0478 0 Td
(we)Tj
1.3323 0 Td
(compared)Tj
4.2406 0 Td
(the)Tj
1.4683 0 Td
(expression)Tj
4.4674 0 Td
(levels)Tj
2.3754 0 Td
(of)Tj
/F12 1 Tf
1.0148 0 Td
[( )7()]TJ
/F8 1 Tf
(.)Tj
-36.4419 -1.2982 Td
(25,000)Tj
2.8232 0 Td
(genes)Tj
2.4435 0 Td
(from)Tj
2.2053 0 Td
(genistein-)Tj
4.1726 0 Td
(and)Tj
1.7291 0 Td
(vehicle-treated)Tj
6.1115 0 Td
(keratinocytes.)Tj
5.7543 0 Td
(Gene)Tj
2.33 0 Td
(expression)Tj
4.4674 0 Td
(data)Tj
1.9106 0 Td
(have)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 399.7984 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Isoflavone)Tj
4.6984 0 Td
(genistein)Tj
4.1386 0 Td
(in)Tj
0.978 0 Td
(the)Tj
1.5874 0 Td
(epithelial)Tj
4.0748 0 Td
(cell)Tj
1.6867 0 Td
(line)Tj
1.7362 0 Td
(HaCaT)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01922)Tj
4.089 0 Td
(97)Tj
0 g
2.0906 0 Td
(February)Tj
4.1599 0 Td
(14,)Tj
1.5874 0 Td
(2018)Tj
33.1585 0 Td
(3)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
61 0 obj
<>stream
endstream
endobj
62 0 obj
<>stream
endstream
endobj
63 0 obj
<>stream
BT
66.402 0 Td
(27)Tj
ET
Q
endstream
endobj
64 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 13 0 R/Annots 69 0 R/Contents 70 0 R/TrimBox[0 0 612 792]>>
endobj
67 0 obj
<>
endobj
71 0 obj
<>stream
/CIDInit/ProcSet findresource begin
12 dict begin begincmap
/CMapName/Adobe-Identity-UCS def
/CIDSystemInfo<>def
/CMapType 2 def
1 begincodespacerange
<0000>
endcodespacerange
4 beginbfchar
<0024><0041>
<0026><0043>
<002A><0047>
<0037><0054>
endbfchar
endcmap
CMapName currentdict /CMap defineresource pop end end
endstream
endobj
72 0 obj
<>/FontDescriptor 73 0 R/DW 600>>
endobj
73 0 obj
<>
endobj
74 0 obj
<>stream
cvt a &@ fpgm62 h glyf&e5