TIMP3 is a CLOCK-dependent diurnal gene that inhibits the expression of UVB-induced inflammatory cytokines in human keratinocytes.

As the outermost physical barrier of an organism, the skin is diurnally exposed to UV radiation (UVR). Recent studies have revealed that the skin exhibits a circadian rhythm in various functions, and this oscillation is disturbed and reset via a strong environmental cue, the UVR. However, a molecular link between circadian perturbation by UVR and UVR-induced cellular responses has not been investigated. We identified tissue inhibitor of metalloproteinase ( TIMP)- 3 as a novel circadian locomotor output cycles kaput (CLOCK)-dependent diurnal gene by using a CLOCK-knockdown strategy in human keratinocytes. Among dozens of identified transcripts down-regulated by CLOCK knockdown, TIMP3 displayed a rhythmic expression in a CLOCK-dependent manner, in which the expression of matrix metalloproteinase (MMP)-1 and inflammatory cytokines, such as TNF-α, chemokine (C-X-C motif) ligand (CXCL)-1, and IL-8, were inversely regulated. Upon UVB exposure, the expression of CLOCK and TIMP3 was down-regulated, which led to an up-regulation of secretion of MMP1 and TNF-α proteins and in the transcription of CXCL1 and IL-8 via CCAAT-enhancer binding protein (C/EBP)-α. UVB-induced TNF-α secretion increased further or decreased by knockdown or overexpression of TIMP3, respectively, as well as by CLOCK. As a novel CLOCK-dependent diurnal gene, TIMP3 inhibits the expression of inflammatory cytokines that are up-regulated by UV irradiation in human keratinocytes. Thus, our work suggests a molecular link between circadian perturbation by UVR and UVR-induced inflammation.-Park, S., Kim, K., Bae, I.-H., Lee, S. H., Jung, J., Lee, T. R., Cho, E.-G. TIMP3 is a CLOCK-dependent diurnal gene that inhibits the expression of UVB-induced inflammatory cytokines in human keratinocytes.

S-nitrosylation of fatty acid synthase regulates its activity through dimerization.

NO regulates a variety of physiological processes, including cell proliferation, differentiation, and inflammation. S-nitrosylation, a NO-mediated reversible protein modification, leads to changes in the activity and function of proteins. In particular, the role of S-nitrosylation during adipogenesis is largely unknown. We hypothesized that the normal physiological levels of NO, but not the excess levels generated under severe conditions, such as inflammation, may be critically involved in the proper regulation of adipogenesis. We found that endogenous S-nitrosylation of proteins was required for adipocyte differentiation. By performing a biotin-switch assay, we identified FAS, a key lipogenic enzyme in adipocytes, as a target of S-nitrosylation during adipogenesis. Interestingly, we also observed that the dimerization of FAS increased in parallel with the amount of S-nitrosylated FAS during adipogenesis. In addition, we found that exogenous NO enhanced the dimerization and the enzymatic activity of FAS. Moreover, site-directed mutagenesis of three predicted S-nitrosylation sites indicated that S-nitrosylation of FAS at Cys(1471)and Cys(2091), but not at Cys(1127), increased its enzymatic activity. Taken together, these results suggest that the S-nitrosylation of FAS at normal physiological levels of NO increases its activity through dimerization and may contribute to the proper regulation of adipogenesis.

Lipin-1 expression is critical for keratinocyte differentiation.

Lipin-1 is an Mg(2+)-dependent phosphatidate phosphatase that facilitates the dephosphorylation of phosphatidic acid to generate diacylglycerol. Little is known about the expression and function of lipin-1 in normal human epidermal keratinocytes (NHEKs). Here, we demonstrate that lipin-1 is present in basal and spinous layers of the normal human epidermis, and lipin-1 expression is gradually downregulated during NHEK differentiation. Interestingly, lipin-1 knockdown (KD) inhibited keratinocyte differentiation and caused G1 arrest by upregulating p21 expression. Cell cycle arrest by p21 is required for commitment of keratinocytes to differentiation, but must be downregulated for the progress of keratinocyte differentiation. Therefore, reduced keratinocyte differentiation results from sustained upregulation of p21 by lipin-1 KD. Lipin-1 KD also decreased the phosphorylation/activation of protein kinase C (PKC)α, whereas lipin-1 overexpression increased PKCα phosphorylation. Treatment with PKCα inhibitors, like lipin-1 KD, stimulated p21 expression, while lipin-1 overexpression reduced p21 expression, implicating PKCα in lipin-1-induced regulation of p21 expression. Taken together, these results suggest that lipin-1-mediated downregulation of p21 is critical for the progress of keratinocyte differentiation after the initial commitment of keratinocytes to differentiation induced by p21, and that PKCα is involved in p21 expression regulation by lipin-1.

Hypoxia leads to abnormal epidermal differentiation via HIF-independent pathways.

Atmospheric oxygen is important for the epidermis, as the skin epidermis is not greatly affected by blood circulation. Therefore, it is necessary to understand the effect of hypoxic signals on the epidermis as some environmental stimuli can induce skin hypoxia. Here, we investigated how hypoxia (1% O2) affected skin equivalents (SEs) and normal human epidermal keratinocytes. We found that hypoxia specifically decreased the protein levels of keratin 1 (K1)/keratin 10 (K10), a representative marker of the epidermal spinous layer in the epidermis. However, hypoxia-inducible factors, the major regulators of hypoxia, did not affect hypoxia-induced down-regulation of K1/K10. We also found that N-acetyl-l-cysteine (NAC), a reactive oxygen species scavenger, antagonized the hypoxia-induced reduction of K1/K10 in keratinocytes and SEs. In contrast to the findings for NAC, inhibitors that blocked reactive oxygen species generation did not cause recovery of K1/K10 protein levels under hypoxic conditions. Taken together, these results indicate that hypoxia leads to abnormal keratinocyte differentiation by down-regulating K1/K10 and that this phenomenon can be ameliorated by NAC.

Human Dermal Stem/Progenitor Cell-Derived Conditioned Medium Improves Senescent Human Dermal Fibroblasts.

Adult skin stem cells are recognized as potential therapeutics to rejuvenate aged skin. We previously demonstrated that human dermal stem/progenitor cells (hDSPCs) with multipotent capacity could be enriched from human dermal fibroblasts using collagen type IV. However, the effects of hDSPCs on cellular senescence remain to be elucidated. In the present study, we investigated whether conditioned medium (CM) collected from hDSPC cultures (hDSPC-CM) exhibits beneficial effects on senescent fibroblasts. We found that hDSPC-CM promoted proliferation and decreased the expression level of senescence-associated ß-galactosidase in senescent fibroblasts. In addition, p53 phosphorylation and p21 expression were significantly reduced in senescent fibroblasts treated with hDSPC-CM. hDSPC-CM restored the expression levels of collagen type I, collagen type III, and tissue inhibitor of metalloproteinase, and antagonized the increase of matrix metalloproteinase 1 expression. Finally, we demonstrated that hDSPC-CM significantly reduced reactive oxygen species levels by specifically up-regulating the expression level of superoxide dismutase 2. Taken together, these data suggest that hDSPC-CM can be applied as a potential therapeutic agent for improving human aged skin.

Epigallocatechin-3-O-(3-O-methyl)-gallate-induced differentiation of human keratinocytes involves klotho-mediated regulation of protein kinase-cAMP responsive element-binding protein signaling.

(-)-Epigallocatechin-3-O-gallate (EGCG) has long been known as a potent inducer of keratinocyte differentiation. Although its molecular mechanisms have been extensively studied, its actions on human skin remain to be elucidated. In this study, we demonstrated that methylated EGCG and EGCG increase the expression of klotho, and that klotho functions as a downstream target of EGCG and methylated EGCG in keratinocyte differentiation. We demonstrated that methylated EGCG3 and EGCG induce morphological changes in normal human epidermal keratinocytes (NHEKs) that are related to up-regulation of klotho expression. We also demonstrated that a klotho-induced keratinocyte differentiation marker in NHEKs is inhibited by H-89, a protein kinase (PKA) inhibitor. These results suggest that methylated EGCG and EGCG may function as inducers of keratinocyte differentiation via transcriptional regulation of the klotho protein.

The Anti-Diabetic Pinitol Improves Damaged Fibroblasts.

Pinitol (3-O-Methyl-D-chiro-inositol) has been reported to possess insulin-like effects and is known as one of the anti-diabetic agents to improve muscle, liver, and endothelial cells. However, the beneficial effects of pinitol on the skin are not well known. Here, we investigated whether pinitol had effects on human dermal fibroblasts (HDFs), and human dermal equivalents (HDEs) irradiated with ultraviolet A (UVA), which causes various damages including photodamage in the skin. We observed that pinitol enhanced wound healing in UVA-damaged HDFs. We also found that pinitol significantly antagonized the UVA-induced up-regulation of matrix metalloproteinase 1 (MMP1), and the UVA-induced down-regulation of collagen type I and tissue inhibitor of metalloproteinases 1 (TIMP1) in HDEs. Electron microscopy analysis also revealed that pinitol remarkably increased the number of collagen fibrils with regular banding patterns in the dermis of UVA-irradiated human skin equivalents. Pinitol significantly reversed the UVA-induced phosphorylation levels of ERK and JNK but not p38, suggesting that this regulation may be the mechanism underlying the pinitol-mediated effects on UVA-irradiated HDEs. We also observed that pinitol specifically increased Smad3 phosphorylation, which is representative of the TGF-ß signaling pathway for collagen synthesis. These data suggest that pinitol exerts several beneficial effects on UVA-induced damaged skin and can be used as a therapeutic agent to improve skin-related diseases.

Blood type B antigen modulates cell migration through regulating cdc42 expression and activity in HaCaT cells.

ABO blood group is determined by carbohydrate antigens, called ABH antigens. It has been known that the change of carbohydrate antigen expression, including ABH antigens, has correlation with the tumor metastasis and survival; however, the exact mechanism remains to be elucidated. ABH antigens are expressed not only in blood cells but also in several tissues. In epidermis, ABH antigen is expressed in the uppermost spinous and granular layer. We investigated the role of ABH antigens on the cell migration of HaCaT keratinocytes, which express B antigen. Knock-down of B antigen expression by small interference RNA of FUT1 inhibited HaCaT cell migration. At that time, we found that lamellipodia and actin fiber were also reduced by knock-down of B antigen expression. The transcription of cdc42, a kind of Rho GTPase which plays a key role in actin polymerization, was reduced by down-regulated B antigen expression. Furthermore, the reduced B antigen expression also inhibited the interaction of cdc42 and N-WASP. Collectively, our data provide a clue how ABH antigens regulate the cell migration mechanism.

Resveratrol induces autophagy through death-associated protein kinase 1 (DAPK1) in human dermal fibroblasts under normal culture conditions.

Autophagy is an essential process degrading damaged components. Although resveratrol has various beneficial activities for health, little is known about the effects of resveratrol on autophagy in skin. We investigated whether resveratrol affects autophagy in human dermal fibroblasts grown in complete medium. We found that after the resveratrol treatment, LC3-II reached a maximum level at 8 h and then gradually decreased. By PCR array analysis, we identified death-associated protein kinase 1 (DAPK1) as a new target of resveratrol, and we confirmed that the expression level of DAPK1 was enhanced by resveratrol. We also demonstrated that DAPK1 knock-down by siRNA was sufficient to reduce resveratrol-induced autophagy but did not affect the phosphorylation level of AMP-activated kinase (AMPK), a well-known target of resveratrol. These data indicate that resveratrol-induced autophagy can be mediated by DAPK1, raising the possibility that some of the beneficial effects of resveratrol may be due to its regulation of DAPK1.

Acute UV irradiation increases heparan sulfate proteoglycan levels in human skin.

Glycosaminoglycans are important structural components in the skin and exist as various proteoglycan forms, except hyaluronic acid. Heparan sulfate (HS), one of the glycosaminoglycans, is composed of repeated disaccharide units, which are glucuronic acids linked to an N-acetyl-glucosamine or its sulfated forms. To investigate acute ultraviolet (UV)-induced changes of HS and HS proteoglycans (HSPGs), changes in levels of HS and several HSPGs in male human buttock skin were examined by immunohistochemistry and real-time quantitative polymerase chain reaction (qPCR) after 2 minimal erythema doses (MED) of UV irradiation (each n = 4-7). HS staining revealed that 2 MED of UV irradiation increased its expression, and staining for perlecan, syndecan-1, syndecan-4, CD44v3, and CD44 showed that UV irradiation increased their protein levels. However, analysis by real-time qPCR showed that UV irradiation did not change mRNA levels of CD44 and agrin, and decreased perlecan and syndecan-4 mRNA levels, while increased syndecan-1 mRNA level. As HS-synthesizing or -degrading enzymes, exostosin-1 and heparanase mRNA levels were increased, but exostosin-2 was decreased by UV irradiation. UV-induced matrix metalloproteinase-1 expression was confirmed for proper experimental conditions. Acute UV irradiation increases HS and HSPG levels in human skin, but their increase may not be mediated through their transcriptional regulation.

Decision Tree-Based Foot Orthosis Prescription for Patients with Pes Planus.

Pes planus, one of the most common foot deformities, includes the loss of the medial arch, misalignment of the rearfoot, and abduction of the forefoot, which negatively affects posture and gait. Foot orthosis, which is effective in normalizing the arch and providing stability during walking, is prescribed for the purpose of treatment and correction. Currently, machine learning technology for classifying and diagnosing foot types is being developed, but it has not yet been applied to the prescription of foot orthosis for the treatment and management of pes planus. Thus, the aim of this study is to propose a model that can prescribe a customized foot orthosis to patients with pes planus by learning from and analyzing various clinical data based on a decision tree algorithm called classification and regressing tree (CART). A total of 8 parameters were selected based on the feature importance, and 15 rules for the prescription of foot orthosis were generated. The proposed model based on the CART algorithm achieved an accuracy of 80.16%. This result suggests that the CART model developed in this study can provide adequate help to clinicians in prescribing foot orthosis easily and accurately for patients with pes planus. In the future, we plan to acquire more clinical data and develop a model that can prescribe more accurate and stable foot orthosis using various machine learning technologies.

Changes in glycosaminoglycans and related proteoglycans in intrinsically aged human skin in vivo.

Glycosaminoglycans (GAGs) and proteoglycans (PGs) are involved in various structural functions and physiological regulations in the skin. To investigate the intrinsic ageing-dependent GAG and PG changes and their gender-specific difference, immunohistochemical stains of several GAGs and PGs were performed in sun-protected buttock skin tissues of young and old, male and female (total n = 32) human skin. Stains of alcian blue, hyaluronic acid (HA) and heparan sulphate were reduced in aged skin in both genders, whereas chondroitin sulphate stain was decreased only in female. Stains of HA synthase-2, CD44, CD44v3, syndecan-1 and decorin were decreased in aged skin in both genders, whereas perlecan stain was reduced only in female, and syndecan-4 stain did not change. Versican stain was increased in male aged skin, but not in female. Age- and gender-related changes in GAGs and PGs in intrinsically aged buttock skin elucidated in this study may play important roles in intrinsic skin ageing process.

Transcriptional regulation of proteoglycans and glycosaminoglycan chain-synthesizing glycosyltransferases by UV irradiation in cultured human dermal fibroblasts.

Various kinds of glycosaminoglycans (GAGs) and proteoglycans (PGs) have been known to be involved in structural and space-filling functions, as well as many physiological regulations in skin. To investigate ultraviolet (UV) radiation-mediated regulation of GAGs and PGs in cultured human dermal fibroblasts, transcriptional changes of many types of PGs and GAG chain-synthesizing enzymes at 18 hr after 75 mJ/cm(2) of UV irradiation were examined using quantitative real-time polymerase chain reaction methods. Hyaluronic acid synthase (HAS)-1, -2, and -3 and hyaluronidase-2 mRNA expressions were significantly increased by UV irradiation. Expressions of lumican, fibromodulin, osteoglycin, syndecan-2, perlecan, agrin, versican, decorin, and biglycan were significantly decreased by UV irradiation, while syndecan-1 was increased. Expressions of GAG chain-synthesizing glycosyltransferases, xylosyltransferase-1, ß1,3-glucuronyltransferase-1, ß1,4-galactosyltransferase-2, -4, exostosin-1, chondroitin polymerizing factor, and chondroitin sulfate synthase-3 were significantly reduced, whereas those of ß1,3-galactosyltransferase-6, ß1,4-galactosyltransferase-3, -7, ß-1,3-N-acetylglucosaminyltran sferase-2, and -7 were increased by UV irradiation. Heparanase-1 mRNA expression was increased, but that of heparanase-2 was reduced by UV irradiation. Time-course investigation of representative genes showed consistent results. In conclusion, UV irradiation may increase hyaluronic acid production through HAS induction, and decrease other GAG productions through downregulation of PG core proteins and GAG chain-synthesizing glycosyltransferases in cultured human dermal fibroblasts.

Rational design of photocatalysts for ammonia production from water and nitrogen gas.

Photocatalytic N2 reduction has emerged as one of the most attractive routes to produce NH3 as a useful commodity for chemicals used in industries and as a carbon-free energy source. Recently, significant progress has been made in understanding, exploring, and designing efficient photocatalyst. In this review, we outline the important mechanistic and experimental procedures for photocatalytic NH3 production. In addition, we review effective strategies on development of photocatalysts. Finally, our analyses on the characteristics and modifications of photocatalysts have been summarized, based on which we discuss the possible future research directions, particularly on preparing more efficient catalysts. Overall, this review provides insights on improving photocatalytic NH3 production and designing solar-driven chemical conversions.

3-Methyladenine Inhibits Procollagen-1 and Fibronectin Expression in Dermal Fibroblasts Independent of Autophagy.

BACKGROUND: Autophagy is deeply associated with aging, but little is known about its association with the extracellular matrix (ECM). 3-methyladenine (3-MA) is a commonly used autophagy inhibitor. OBJECTIVE: We used this compound to investigate the role of autophagy in dermal ECM protein synthesis. METHODS: Normal human dermal fibroblasts (NHDFs) were treated with 3-MA for 24 h, and mRNA encoding several ECM proteins was analyzed in addition to the protein expression of procollagen-1 and fibronectin. Several phosphoinositide 3-kinase (PI3K) inhibitors, an additional autophagy inhibitor, and small interfering RNA (siRNA) targeting autophagy-related genes were additionally used to confirm the role of autophagy in ECM synthesis. RESULTS: Only 3-MA, but not other chemical compounds or autophagy-related genetargeting siRNA, inhibited the transcription of procollagen-1 and fibronectin-encoding genes. Further, 3-MA did not affect the activation of regulatory Smads, but inhibited the interaction between Smad3 with p300. Moreover, 3-MA treatment increased the phosphorylation of cAMP response element-binding protein (CREB); however, CREB knock-down did not recover 3-MA-induced procollagen-1 and fibronectin downregulation. CONCLUSION: We revealed that 3-MA might inhibit procollagen-1 and fibronectin synthesis in an autophagy-independent manner by interfering with the binding between Smad3 and p300. Therefore, 3-MA could be a candidate for the treatment of diseases associated with the accumulation of ECM proteins.

Dynamic body posture after unilateral mastectomy: a pilot study.

BACKGROUND: Postural changes after unilateral mastectomy may appear in relation to the dominant hand, postoperative duration, and dynamic conditions. This study aimed to compare the postural changes by inclination angles and muscle activities in the static and dynamic sitting position between women with breast cancer who underwent mastectomy and women who did not have breast cancer. METHODS: The observational study design was conducted. We evaluated 17 women who underwent modified radical mastectomy (MRM) more than 1 year prior to the study. They were categorized into the Rt. mastectomy group (n=7) and the Lt. mastectomy group (n=10). An aged-matched cohort of 8 healthy females was also included. The inclination angle in both static and dynamic sitting positions was measured using the balance board system (BBS), and the muscle activities of 8 muscles were measured in the dynamic sitting position. RESULTS: There was no significant difference in demographic characteristics between the patients, and all patients were right-handed. The inclination angle of the anterior-posterior axis when leaning forward was significantly increased to the anterior side in the Rt. mastectomy group than in the Lt. mastectomy group. Meanwhile, the inclination angle in the static sitting position and when tilted backward to both directions did not differ among the 3 groups. The inclination angle of the right-left axis was statistically increased to the left side during tilting anterior-left direction in the Rt. Mastectomy group. The muscle activities of the thoracic erector spinae were significantly lower when tilted backward in the Rt. mastectomy group than in the Lt. mastectomy group. CONCLUSIONS: Compared with left mastectomy, right unilateral mastectomy yielded more postural changes under dynamic sitting state in right-handed female patients with breast cancer. Thus, to maintain the trunk balance and prevent the postural changes after unilateral mastectomy, the postoperative exercise programs for the para-thoracic muscles will be helpful.

UVB-dependent inhibition of lipin-1 protects against proinflammatory responses in human keratinocytes.

Lipin-1 is an Mg2+-dependent phosphatidate phosphatase (PAP1) that catalyzes a critical step in the synthesis of glycerophospholipids and is also a cotranscriptional regulator. The role of lipin-1 in the regulation of inflammatory responses has been extensively studied in various cell types but not in skin cells. In the present study, the function of lipin-1 in UVB-induced proinflammatory responses was assessed in normal human epidermal keratinocytes (NHEKs). UVB radiation downregulated lipin-1 expression. Lipin-1 inhibition was mediated by UVB-dependent sterol-response element binding protein-1 (SREBP-1) inhibition. The UVB-dependent inhibition of lipin-1 and SREBP-1 was mediated by AMPK activation. UVB-induced activation of JNK was dependent on AMPK activation and mediated lipin-1 inhibition. Prevention of UVB-mediated lipin-1 repression by introducing a lipin-1 expression vector stimulated IL-6 and IL-8 production, suggesting that lipin-1 inhibition attenuates UVB-induced IL-6 and IL-8 production. The downregulation of lipin-1 ameliorated UVB-induced NF-ĸB phosphorylation, which might be attributed to the suppression of UVB-induced accumulation of free fatty acids (FFAs). Pharmacological inhibition of PAP1 with propranolol suppressed UVB-induced production of IL-6 and IL-8 in NHEKs and reconstituted human skin models. Taken together, lipin-1 is downregulated by exposure to UVB radiation, which confers protection against UVB-induced proinflammatory responses; therefore, the inhibition of lipin-1 is a potential strategy for photoaging.

Long exposure of non-cytotoxic concentrations of methylselenol suppresses the invasive potential of B16F10 melanoma.

To assess the inhibitory effects of methylselenol on the invasion of murine B16F10 melanoma cells, we carried out in vivo and in vitro experiments using Se-methylselenocysteine (Se-MSC) and selenomethionine (SeMet), respectively. In an animal experiment, the supplementation of drinking water with Se-MSC (4 ppm Se) led to a significant increase in Se levels in the lung, liver and serum in mice. Mice given a mash diet or water supplemented with Se-MSC (2, 4 and 6 ppm Se in the mash diet, and 2 and 4 ppm Se in the drinking water) displayed an almost completely diminished pulmonary metastasis of B16F10 melanoma cells and an enhanced survival, compared to the control mice which were given a basal diet. Treatment with non-cytotoxic concentrations of SeMet (2.5, 5 and 10 microM plus 0.02 U/ml METase, methioninase) induced a substantial decrease in the expression of integrin alphavbeta3, the FN receptor and adhesion ability to vitronectin (VN) and fibronectin (FN) in B16F10 melanoma cells. Moreover, these compounds suppressed gelatinase activity, invasive ability and wound migration in the culture system. SeMet-METase prevented the conversion of pro-MMP-9 to its active form and decreased pro-MMP-2 activities in a zymogram. The pre-treatment of B16F10 melanoma cells with SeMet-METase led to a decrease in pulmonary metastasis and extended survival in mice injected with tumor cells. Collectively, our results indicate that integrin expression is crucial in promoting the metastatic phenotype in murine B16F10 melanoma cells by supporting specific adhesive and invasive properties, suggesting that Se-MSC effectively reduces the metastasis of B16F10 melanoma cells as a nutritional adjuvant. Methylselenol may also contribute to the suppression of integrin expression.

Influence of pelvic asymmetry and idiopathic scoliosis in adolescents on postural balance during sitting.

The effects of pelvic asymmetry and idiopathic scoliosis on postural balance during sitting were studied by measuring inclination angles, pressure distribution, and electromyography. Participants were classified into a control group, pelvic asymmetry group, scoliosis group, and scoliosis with pelvic asymmetry and then performed anterior, posterior, left, and right pelvic tilting while sitting on the unstable board for 5 seconds to assess their postural balance. Inclination and obliquity angles between the groups were measured by an accelerometer located on the unstable board. Pressure distribution (maximum force and peak pressure) was analyzed using a capacitive seat sensor. In addition, surface electrodes were attached to the abdominal and erector spinae muscles of each participant. Inclination and obliquity angles increased more asymmetrically in participants with both pelvic asymmetry and scoliosis than with pelvic asymmetry or scoliosis alone. Maximum forces and peak pressures of each group showed an asymmetrical pressure distribution caused by the difference in height between the left and right pelvis and curve type of the patients' spines when performing anterior, posterior, left, and right pelvic tilting while sitting. Muscle contraction patterns of external oblique, thoracic erector spinae, lumbar erector spinae, and lumbar multifidus muscles may be influenced by spine curve type and region of idiopathic scoliosis. Asymmetrical muscle activities were observed on the convex side of scoliotic patients and these muscle activity patterns were changed by the pelvic asymmetry. From these results, it was confirmed that pelvic asymmetry and idiopathic scoliosis cause postural asymmetry, unequal weight distribution, and muscular imbalance during sitting.

miR-526b targets 3' UTR of MMP1 mRNA.

Regulation of matrix metalloproteinases (MMPs) is important for many physiological processes involving cancers, inflammation, tissue remodeling and skin aging. Here, we report the novel finding that the expression of MMP1 mRNA is downregulated by the overexpression of miR-526b which is a member of chromosome 19 microRNA cluster (C19MC). Our analysis using reporter constructs containing the 3' untranslated region (3' UTR) of MMP1 and its mutant form showed that the region from 377-383 in the 3' UTR of MMP1 is critical for targeting by miR-526b. In addition, the expression pattern of miR-526b and MMP1 mRNA showed reverse relation between adult dermal and neonatal fibroblasts. We show for the first time that miR-526b, an miRNA belonging to C19MC, can target the 377-383 region of the MMP1 3' UTR.