Skin toxicity is a common symptom of anti-epidermal rowth factor receptor(EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced ...Skin toxicity is a common symptom of anti-epidermal rowth factor receptor(EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced by such antibodies negatively impact on the quality of life of patients and decreases drug compliance during treatment. If we can predict the high-risk group susceptible to severe skin toxicity before treatment, we can undertake the early management of any arising skin disorders and formulate a more accurate prognosis for anti-EGFR antibody treatment. Previous studies have identified molecular markers of skin toxicity induced by anti-EGFR antibody, such as EGFR polymorphisms, the expression of inflammatory chemokines and serum levels of EGFR ligands. A clinical trial was undertaken involving the escalation of cetuximab doses, guided by the grade of skin toxicity observed, such as no or low-grade, in metastatic colorectal cancer(the EVEREST study). The dose escalation of cetuximab was confirmed by a safety profile and had the tendency to achieve a higher response rate in KRAS wild-type patients. A large, prospective randomized trial is now ongoing(EVEREST 2) and the results of this trial may contribute to personalized medicine in KRAS wild-type colorectal cancer patients.展开更多
Beyond regulation of male sexual function, the increasing evidence shows that androgens and androgen receptor (AR) have a variety of physiological and pathological effects on the skin. Skin cells express all androgen ...Beyond regulation of male sexual function, the increasing evidence shows that androgens and androgen receptor (AR) have a variety of physiological and pathological effects on the skin. Skin cells express all androgen metabolizing enzymes that are required for independent skin androgen synthesis and the development of hyperandrogenic related disorders such as acne, hirsutism and androgenetic alopecia. Targeting various elements of androgen function and metabolism is the major goal of medication design for the treatment of androgen-related diseases. Antiandrogen drugs such as clascoterone, flutamide could improve conditions. Even though the involvement of androgens and AR in skin diseases has been investigated for a long time, their molecular mechanisms in skin disorders remain largely insufficient. In this review, recent studies and advances on the role of androgens/AR in several skin-related diseases and their therapeutics are systematically summarized.展开更多
The P2X7 receptor is a trimeric ligand-gated cation channel present on immune and other cells. Activation of this receptor by its natural ligand extracellular adenosine triphosphate results in a variety of downstream ...The P2X7 receptor is a trimeric ligand-gated cation channel present on immune and other cells. Activation of this receptor by its natural ligand extracellular adenosine triphosphate results in a variety of downstream responses, including the release of pro-inflammatory mediators and cell death. In normal skin, P2X7 is present on keratinocytes, Langerhans cells and fibroblasts, while the presence of this receptor on other cutaneous cells is mainly inferred from studies of equivalent cell types present in other tissues. Mast cells in normal skin however express negligible amounts of P2X7, which can be upregulated in cutaneous disease. This review discusses the potential significance of P2X7 in skin biology, and the role of this receptor in inflammatory skin disorders such as irritant and chronic dermatitis, psoriasis, graft-versus-host disease, as well is in wound healing, transplantation and skin cancer.展开更多
清道夫受体B类成员1(scavenger receptor class B member 1,Scarb1)作为细胞表面的膜受体蛋白,在动物体色形成过程中发挥重要作用。为了解Scarb1基因在虹鳟(Oncorhynchus mykiss)体色形成中的作用,通过RACE技术克隆虹鳟Scarb1基因的cDN...清道夫受体B类成员1(scavenger receptor class B member 1,Scarb1)作为细胞表面的膜受体蛋白,在动物体色形成过程中发挥重要作用。为了解Scarb1基因在虹鳟(Oncorhynchus mykiss)体色形成中的作用,通过RACE技术克隆虹鳟Scarb1基因的cDNA全长,并运用生物信息学方法分析该基因及其序列结构特征,同时使用实时定量PCR(qRT-PCR)检测Scarb1基因在虹鳟、金鳟及其杂交F_(1)代不同发育阶段和不同组织中的表达情况。结果显示,Scarb1基因cDNA序列全长为2032 bp,开放阅读框1479 bp,编码492个氨基酸,预测分子质量为55.59 ku,且存在保守的CD36结构域和2个跨膜区。序列同源性分析显示,虹鳟与其他硬骨鱼类的氨基酸序列相似度为71.69%~98.58%;进化分析发现虹鳟与大马哈鱼亲缘关系最近,与哺乳动物和两栖动物亲缘关系最远。qRT-PCR检测结果表明,在虹鳟与金鳟胚胎期及出膜后各发育阶段中Scarb1基因均有不同程度表达,且表现为受精期至桑葚期的表达显著高于其他时期(P<0.05),对虹鳟与金鳟同一时期的差异分析发现该基因在胚胎期及7 dph(days post hatch)、1 M(month post hatch)、2 M和3 M时期中表达存在显著差异(P<0.01)。Scarb1基因在虹鳟与金鳟背部皮肤和背部肌肉等色素沉着性组织中表达量较高,其中在金鳟背部皮肤的表达量显著高于虹鳟(P<0.01)。此外,Scarb1基因在杂交F_(1)代不同发育时期中的表达规律与双亲一致;在不同组织中,该基因在杂交F_(1)代背部皮肤中的表达量介于双亲之间。研究结果表明,Scarb1基因与虹鳟体色形成有着密切关系,且可能在金鳟黄色体色形成过程中发挥重要作用。展开更多
The histological characteristics,distribution and variability of epidermal growth factor(EGF) and epidermal growth factor receptor(EGFR) during development of skin in the goat fetus were studied with histological and ...The histological characteristics,distribution and variability of epidermal growth factor(EGF) and epidermal growth factor receptor(EGFR) during development of skin in the goat fetus were studied with histological and immunohistochemical methods.The results showed that the epidermis formed at the 6th gestational week,the thickness increased gradually because of transition from simple epithelium to stratified epithelium,and then decreased after the 15th week.The dermis was present at the 10th week,and the dermal derivatives appeared after the 11th week.All structures of the skin matured gradually during prenatal development.Low expression of EGF and EGFR could be observed at the 6th week and increased thereafter.Before the 11th week,EGF was mainly located in the cytoplasm of the basal layer of cells of epidermis,hair follicular epithelial cells and fibroblasts,and EGFR was mainly located on cell membranes of these cells.From the 11th to 16th week,the expression of EGF and EGFR extended from basal layer cells,prickle cells,hair follicular epithelial cells and fibroblasts to vascular endothelial cells,epithelial cells of sweat glands and arrector pili muscle.EGF was mainly detected cytoplasmically,and EGFR was located on membranes of these cells.From the 17th week to birth,EGF was mainly located in cells of the basal layer and hair follicular epithelial cells as the skin thinned and staining intensity continued to increase.The expressed amount of EGF and EGFR tended to increase throughout the whole development stage encompassed by gestational weeks 6 to 21 and the two components of the EGF signaling system were highly correlated.The results suggest that EGF and EGFR play important roles in the development of skin and its derivatives.展开更多
Estrogen is essential for the skin to maintain its physiological function. The binding of estrogen to the estrogen receptor (ER) activates gene transcription, which has biological effects on the target tissue. Estroge...Estrogen is essential for the skin to maintain its physiological function. The binding of estrogen to the estrogen receptor (ER) activates gene transcription, which has biological effects on the target tissue. Estrogen levels and ER expression are known to decrease with aging and exposure to ultraviolet light (UV);therefore, increased estrogen levels and ER expression may improve age-related changes in the skin. <em>Rehmannia</em> root has been reported to have blood circulation-promoting and anti-inflammatory effects;however, few studies have reported the effects of <em>Rehmannia</em> root on skin. In this study, we examined the effects of <em>Rehmannia glutinosa</em> Libosch. var. purpurea Makino root extract (RE) on ER expression, and estrogen, RE, or their related ingredients increased ER expression in human epidermal keratinocytes, human dermal fibroblasts, and skin models. Moreover, RE increased the production of basic fibroblast growth factor, transforming growth factor <em>β</em>1, and epidermal growth factor. The mixture of estrogen and RE improved extracellular matrix (ECM) production to a greater degree than estrogen and RE independently. Although high population doubling levels (PDL) and UV irradiation downregulated ER expression, RE upregulated ER expression in high PDL cells and UV irradiated cells. In addition, RE increased the expression of epidermal differentiation marker proteins compared to their expression levels in the absence of RE. The collective findings suggest that RE aids in the prevention of skin aging by upregulating the ER expression that has been decreased by aging and UV and promoting estrogen activity, ECM production, and epidermal differentiation.展开更多
The aim of this study was to clarify the response of sympathetic activity to antihypertensive drugs using a mental stress test in hypertensive patients and to determine the effects of antihypertensive drugs on the sym...The aim of this study was to clarify the response of sympathetic activity to antihypertensive drugs using a mental stress test in hypertensive patients and to determine the effects of antihypertensive drugs on the sympathetic activitymediated hemodynamic response to mental stress. Hypertensive patients were divided into three groups according to the type of drug(s) being taken: a calcium antagonist group, an angiotensin II receptor blocker group, and a combination therapy group of calcium antagonists and angiotensin II receptor blockers. The Stroop color-word conflict test was applied as a mental stress test and hemodynamic responses to mental stress were measured, including blood pressure, pulse rate, and skin blood flow. Elevation of blood pressure by mental stress was suppressed in the combination therapy group compared with the calcium antagonist group. Reduction of skin blood flow by mental stress was suppressed in both the angiotensin II blocker group and the combination therapy group compared with the calcium antagonist group. In conclusion, skin blood flow can be a useful tool to evaluate sympathetic activity and combination therapy with calcium antagonists and angiotensin II receptor blockers were the most useful therapy for suppressing the hemodynamic response to mental stress.展开更多
文摘Skin toxicity is a common symptom of anti-epidermal rowth factor receptor(EGFR) antibody treatment and is also a predictive marker of its efficacy in colorectal cancer patients. However, severe skin disorders induced by such antibodies negatively impact on the quality of life of patients and decreases drug compliance during treatment. If we can predict the high-risk group susceptible to severe skin toxicity before treatment, we can undertake the early management of any arising skin disorders and formulate a more accurate prognosis for anti-EGFR antibody treatment. Previous studies have identified molecular markers of skin toxicity induced by anti-EGFR antibody, such as EGFR polymorphisms, the expression of inflammatory chemokines and serum levels of EGFR ligands. A clinical trial was undertaken involving the escalation of cetuximab doses, guided by the grade of skin toxicity observed, such as no or low-grade, in metastatic colorectal cancer(the EVEREST study). The dose escalation of cetuximab was confirmed by a safety profile and had the tendency to achieve a higher response rate in KRAS wild-type patients. A large, prospective randomized trial is now ongoing(EVEREST 2) and the results of this trial may contribute to personalized medicine in KRAS wild-type colorectal cancer patients.
文摘Beyond regulation of male sexual function, the increasing evidence shows that androgens and androgen receptor (AR) have a variety of physiological and pathological effects on the skin. Skin cells express all androgen metabolizing enzymes that are required for independent skin androgen synthesis and the development of hyperandrogenic related disorders such as acne, hirsutism and androgenetic alopecia. Targeting various elements of androgen function and metabolism is the major goal of medication design for the treatment of androgen-related diseases. Antiandrogen drugs such as clascoterone, flutamide could improve conditions. Even though the involvement of androgens and AR in skin diseases has been investigated for a long time, their molecular mechanisms in skin disorders remain largely insufficient. In this review, recent studies and advances on the role of androgens/AR in several skin-related diseases and their therapeutics are systematically summarized.
文摘The P2X7 receptor is a trimeric ligand-gated cation channel present on immune and other cells. Activation of this receptor by its natural ligand extracellular adenosine triphosphate results in a variety of downstream responses, including the release of pro-inflammatory mediators and cell death. In normal skin, P2X7 is present on keratinocytes, Langerhans cells and fibroblasts, while the presence of this receptor on other cutaneous cells is mainly inferred from studies of equivalent cell types present in other tissues. Mast cells in normal skin however express negligible amounts of P2X7, which can be upregulated in cutaneous disease. This review discusses the potential significance of P2X7 in skin biology, and the role of this receptor in inflammatory skin disorders such as irritant and chronic dermatitis, psoriasis, graft-versus-host disease, as well is in wound healing, transplantation and skin cancer.
文摘清道夫受体B类成员1(scavenger receptor class B member 1,Scarb1)作为细胞表面的膜受体蛋白,在动物体色形成过程中发挥重要作用。为了解Scarb1基因在虹鳟(Oncorhynchus mykiss)体色形成中的作用,通过RACE技术克隆虹鳟Scarb1基因的cDNA全长,并运用生物信息学方法分析该基因及其序列结构特征,同时使用实时定量PCR(qRT-PCR)检测Scarb1基因在虹鳟、金鳟及其杂交F_(1)代不同发育阶段和不同组织中的表达情况。结果显示,Scarb1基因cDNA序列全长为2032 bp,开放阅读框1479 bp,编码492个氨基酸,预测分子质量为55.59 ku,且存在保守的CD36结构域和2个跨膜区。序列同源性分析显示,虹鳟与其他硬骨鱼类的氨基酸序列相似度为71.69%~98.58%;进化分析发现虹鳟与大马哈鱼亲缘关系最近,与哺乳动物和两栖动物亲缘关系最远。qRT-PCR检测结果表明,在虹鳟与金鳟胚胎期及出膜后各发育阶段中Scarb1基因均有不同程度表达,且表现为受精期至桑葚期的表达显著高于其他时期(P<0.05),对虹鳟与金鳟同一时期的差异分析发现该基因在胚胎期及7 dph(days post hatch)、1 M(month post hatch)、2 M和3 M时期中表达存在显著差异(P<0.01)。Scarb1基因在虹鳟与金鳟背部皮肤和背部肌肉等色素沉着性组织中表达量较高,其中在金鳟背部皮肤的表达量显著高于虹鳟(P<0.01)。此外,Scarb1基因在杂交F_(1)代不同发育时期中的表达规律与双亲一致;在不同组织中,该基因在杂交F_(1)代背部皮肤中的表达量介于双亲之间。研究结果表明,Scarb1基因与虹鳟体色形成有着密切关系,且可能在金鳟黄色体色形成过程中发挥重要作用。
基金supported by Natural Science Foundation of Shanxi Province of China(2004C120)Talent Foundation of Northwest A&F University
文摘The histological characteristics,distribution and variability of epidermal growth factor(EGF) and epidermal growth factor receptor(EGFR) during development of skin in the goat fetus were studied with histological and immunohistochemical methods.The results showed that the epidermis formed at the 6th gestational week,the thickness increased gradually because of transition from simple epithelium to stratified epithelium,and then decreased after the 15th week.The dermis was present at the 10th week,and the dermal derivatives appeared after the 11th week.All structures of the skin matured gradually during prenatal development.Low expression of EGF and EGFR could be observed at the 6th week and increased thereafter.Before the 11th week,EGF was mainly located in the cytoplasm of the basal layer of cells of epidermis,hair follicular epithelial cells and fibroblasts,and EGFR was mainly located on cell membranes of these cells.From the 11th to 16th week,the expression of EGF and EGFR extended from basal layer cells,prickle cells,hair follicular epithelial cells and fibroblasts to vascular endothelial cells,epithelial cells of sweat glands and arrector pili muscle.EGF was mainly detected cytoplasmically,and EGFR was located on membranes of these cells.From the 17th week to birth,EGF was mainly located in cells of the basal layer and hair follicular epithelial cells as the skin thinned and staining intensity continued to increase.The expressed amount of EGF and EGFR tended to increase throughout the whole development stage encompassed by gestational weeks 6 to 21 and the two components of the EGF signaling system were highly correlated.The results suggest that EGF and EGFR play important roles in the development of skin and its derivatives.
文摘Estrogen is essential for the skin to maintain its physiological function. The binding of estrogen to the estrogen receptor (ER) activates gene transcription, which has biological effects on the target tissue. Estrogen levels and ER expression are known to decrease with aging and exposure to ultraviolet light (UV);therefore, increased estrogen levels and ER expression may improve age-related changes in the skin. <em>Rehmannia</em> root has been reported to have blood circulation-promoting and anti-inflammatory effects;however, few studies have reported the effects of <em>Rehmannia</em> root on skin. In this study, we examined the effects of <em>Rehmannia glutinosa</em> Libosch. var. purpurea Makino root extract (RE) on ER expression, and estrogen, RE, or their related ingredients increased ER expression in human epidermal keratinocytes, human dermal fibroblasts, and skin models. Moreover, RE increased the production of basic fibroblast growth factor, transforming growth factor <em>β</em>1, and epidermal growth factor. The mixture of estrogen and RE improved extracellular matrix (ECM) production to a greater degree than estrogen and RE independently. Although high population doubling levels (PDL) and UV irradiation downregulated ER expression, RE upregulated ER expression in high PDL cells and UV irradiated cells. In addition, RE increased the expression of epidermal differentiation marker proteins compared to their expression levels in the absence of RE. The collective findings suggest that RE aids in the prevention of skin aging by upregulating the ER expression that has been decreased by aging and UV and promoting estrogen activity, ECM production, and epidermal differentiation.
文摘The aim of this study was to clarify the response of sympathetic activity to antihypertensive drugs using a mental stress test in hypertensive patients and to determine the effects of antihypertensive drugs on the sympathetic activitymediated hemodynamic response to mental stress. Hypertensive patients were divided into three groups according to the type of drug(s) being taken: a calcium antagonist group, an angiotensin II receptor blocker group, and a combination therapy group of calcium antagonists and angiotensin II receptor blockers. The Stroop color-word conflict test was applied as a mental stress test and hemodynamic responses to mental stress were measured, including blood pressure, pulse rate, and skin blood flow. Elevation of blood pressure by mental stress was suppressed in the combination therapy group compared with the calcium antagonist group. Reduction of skin blood flow by mental stress was suppressed in both the angiotensin II blocker group and the combination therapy group compared with the calcium antagonist group. In conclusion, skin blood flow can be a useful tool to evaluate sympathetic activity and combination therapy with calcium antagonists and angiotensin II receptor blockers were the most useful therapy for suppressing the hemodynamic response to mental stress.
