Jin Ho Chung

Infrared plus visible light and heat from natural sunlight participate in the expression of MMPs and type I procollagen as well as infiltration of inflammatory cell in human skin in vivo

BACKGROUND Compared with the detailed characterization of the ultraviolet (UV) response in human skin, the effects of infrared (IR) and other regions of the sunlight are scarce. OBJECTIVES To determine the participation of IR/visible light and heat components of the sunlight on matrix metalloproteinases (MMPs) and type I procollagen expression, and inflammatory cell infiltration in human skin in vivo. METHODS The buttocks of 16 healthy volunteers (aged 24-43 years, 10 male and 6 female) were irradiated with a 1.1-3 minimal erythema dose (MED) of natural sunlight. To determine the differential effects of UV, IR/visible rays and solar heat alone, the exposed sites were covered with either a UV filter or black cloth, respectively, during irradiation. Skin samples were taken 24h later. RESULTS IR/visible light spectrum of sunlight significantly increased MMP-1 and MMP-9 expression and decreased type I procollagen expression. Solar heat also contributed to the increased MMP-1 expression. Only the UV region recruited neutrophils into the dermis, while UV, IR/visible light and heat contributed to macrophage infiltration. CONCLUSIONS IR/visible light and heat of natural sunlight, in addition to UV, play a role in modulating the expressions of MMPs and procollagen, and inflammatory cell infiltration in human skin.

Doxorubicin-induced platelet cytotoxicity: a new contributory factor for doxorubicin-mediated thrombocytopenia.

Summary.  Background: Doxorubicin (DOX) is a widely used anticancer drug for solid tumors and hematologic malignancy, but its active use is hampered by serious adverse effects, including thrombocytopenia. Although bone marrow toxicity of DOX has been suggested to be the sole mechanism underlying the reduced platelet counts, the direct effects of DOX on platelets have never been examined. Objective: Here, we investigated the DOX‐induced platelet cytotoxicity and its underlying mechanism in an effort to elucidate the contribution of platelet cytotoxicity to DOX‐induced thrombocytopenia. Results: In freshly isolated human platelets, DOX induced platelet cytotoxicity in a time‐dependent and concentration‐dependent manner. Reactive oxygen species (ROS) generation, decreased glutathione levels and subsequent protein thiol depletion were shown to underlie the DOX‐induced platelet cytotoxicity. Conspicuously, DOX‐treated platelets displayed apoptotic features such as caspase‐3 activation, reduced mitochondrial transmembrane potential, and phosphatidylserine exposure. Decreased glutathiolation of procaspase‐3 was shown to be a link between protein thiol depletion and caspase‐3 activation. It is of note that DOX‐mediated platelet cytotoxicity was significantly enhanced by shear stress, a common complicating factor in cancer patients. These in vitro results were further confirmed by an in vivo animal model, where administration of DOX induced a platelet count decrease, ROS generation, caspase‐3 activation, protein thiol depletion, and damaged platelet integrity. Conclusion: We demonstrated that DOX can directly induce platelet cytotoxicity through ROS generation, decreased glutathione levels, and protein thiol depletion. We believe that this study provides important evidence for the role of DOX‐induced platelet cytotoxicity in the development of thrombocytopenia in DOX‐treated patients.

Cholesterol inhibits MMP-9 expression in human epidermal keratinocytes and HaCaT cells

Cholesterol is a major component of skin lipids and acts as a regulator of vesicular trafficking and signal transduction. However, the function of cholesterol on matrix metalloproteinases (MMPs) expression of human skin is not fully understood. Here, we investigated the effects of cholesterol on MMP‐9 expression in normal human keratinocytes (NHK) and HaCaT cells. Basal level of MMP‐9 expression was decreased by cholesterol in NHK. On the other hand, MMP‐9 expression was increased by the cholesterol depletion agent, methyl‐β‐cyclodextrin (MβCD), while it was inhibited by cholesterol repletion in HaCaT cells. MβCD induced ERK and JNK phosphorylation were prevented by cholesterol repletion. The inhibition of ERK and JNK decreased MβCD‐induced MMP‐9 expression. Therefore, our results suggest that cholesterol regulates MMP‐9 expression through ERK and JNK‐dependent pathways.

Triterpenoid saponin fromviola hondoensis W. Becker et H Boss. and their effect on mmp-1 and type i procollagen expression

Bioassay-guided fractionation has led to the isolation of triterpenoid saponins such as Acutoside A (3-O-[O-β-D-glucopyranosyl-(1→2)-O-β-D-glucopyranosyl] oleanolic acid) from the whole plants ofViola hondoensis. Among them, Saponin 1 exhibited potent inhibitory activity against matrix metalloproteinase (MMP)-1, and prevented the UV-induced changes in the MMP-1 expression. In addition, compound was isolated from this plant for the first time.

The effect of curculigoside on the expression of matrix metalloproteinase-1 in cultured human skin fibroblasts

The dried rhizomes of Curculigo orchioides G. yielded two phenolic glycosides, curculigoside (1), orcinol-β-D-glucoside (4), and two cycloartane saponins, curculigosaponin G (2), curculigosaponin I (3). The structures were determined using spectroscopic methods. Among these isolates, compound 1 exhibited potent inhibitory activity against matrix metalloproteinase-1 in cultured human skin fibroblasts. In addition, it increased the level of Bcl-2 protein expression and decreased the level of Bax protein expression. Compound 4 was isolated from this plant for the first time.

Procoagulant and prothrombotic effects of the herbal medicine, Dipsacus asper and its active ingredient, dipsacus saponin C, on human platelets

Background: In spite of the growing popularity of herbal medicines and natural food supplements, their effects on cardiovascular homeostasis remain largely unknown, especially regarding pro‐thrombotic risks.

RETRACTED: The effect of 2′,4′,7-trihydroxyisoflavone on ultraviolet-induced matrix metalloproteinases-1 expression in human skin fibroblasts

Reason: This article has been retracted at the request of the editors and authors due to unreliable data resulting from instrument error.

Triterpenoid from Tiarella polyphylla, regulation of type 1 procollagen and MMP-1 in ultraviolet irradiation of cultured old age human dermal fibroblasts.

Although many studies have been performed to elucidate the molecular consequences of ultraviolet irradiation, little is known about the effect of natural products. Ultraviolet irradiation is widely considered to be an environmental stress. Here we investigated the effect of 3,23-dihy-droxy-20(29)-lupen-27-oic acid on the regulation of MMP-1 and type 1 procollagen in Ultraviolet irradiation of cultured old age human dermal fibroblasts. 3, 23-dihydroxy-20(29)-lupen-27-oic acid was isolated fromTiarella polyphylla D. Don (Saxifragaceae). Among them, 3, 23-dihydroxy-20(29)-lupen-27-oic acid induced the regulation of Type 1- procollagen and reduced the regulation of MMP-1 at the protein levels in a dose-dependent manner by ultraviolet irradiation. Taken together, our results suggest that 3, 23-dihydroxy-20(29)-lupen-27-oic acid plays an important role in the induction of Type 1-procollagen and reduction of MMP-1 by ultraviolet irradiation in old age human dermal fibroblasts.

LB30057 inhibits platelet aggregation and vascular relaxation induced by thrombin.

Previous study showed that an amidrazonophenylalanine derivative, LB30057, which has high water solubility, inhibited the catalytic activity of thrombin potently by interaction with the active site of thrombin. In the current investigation, we examined whether LB30057 inhibited platelet aggregation and vascular relaxation induced by thrombin. Treatment with LB30057 to platelet-rich plasma (PRP) isolated from human blood resulted in a concentration-dependent inhibition of thrombin-induced aggregation. Values for IC50 and IC100 were 54±4 nM and 96±3 nM, respectively. This inhibition was agonist (thrombin) specific, since IC50 values for collagen and ADP were much greater than those for thrombin. In addition, concentration-dependent inhibitory effects were observed on the serotonin secretion induced by thrombin in PRP. Consistent with these findings, thrombin-induced increase in cytosolic calcium levels was inhibited in a concentration-dependent manner. When LB30057 was treated with aortic rings isolated from rats, LB30057 resulted in a concentration-dependent inhibition of thrombin-induced vascular relaxation. All these results suggest that LB30057 is a potent inhibitor of platelet aggregation and blood vessel relaxation induced by thrombin.