皮肤共生菌在皮肤健康和疾病中的作用研究进展

人体皮肤上有多种微生物定居,这些微生物群落的组成、分布和动态变化对皮肤的健康状况和疾病有着重要的调节作用.然而,人们一直不清楚皮肤微生物群落如何影响人类健康.对皮肤共生菌进行深入研究,不仅有助于发现有益皮肤共生菌菌株,也有助于筛选相应皮肤疾病新的药物靶标.近年来,对皮肤共生菌与宿主之间相互影响和作用机制的研究逐渐深入,...     

组织工程皮肤研究现状

组织工程皮肤是通过培养功能细胞,将其与细胞外基质及支架材料互相作用,制成的具有生物活性的人工皮肤替代物。组织工程皮肤的发展为修复皮肤创面,重建皮肤功能,治疗皮肤病提供了新的方法。本文从皮肤种子细胞培养、真皮支架材料和体外构建活性复合皮三个方面对组织工程皮肤的研究进展进行了综述。目前组织工程皮肤在一定程度上克服了原有的皮肤供区不足、免疫排斥、传播疾病等各种问题。新的种子细胞和支架材料逐渐成熟,并逐渐应用于临床治疗;在种子细胞和真皮替代物基础上发展起来的复合皮肤可以更快速的促进缺损皮肤的愈合,但与在体皮肤比较尚有差距。组织工程皮肤是理想的皮肤替代物,具有良好的发展前景,未来的研究应该着眼于模仿机体皮肤的生理结构和功能,使愈合后的皮肤与在体皮肤融为一体。     

慢性湿疹患者皮损、鼻粘膜需氧微生物群的定位、定量研究

本文首次应用定位、定量方法对23例小腿部慢性湿疹患者皮损、邻近皮肤及鼻孔的菌群,从微生态学的角度进行探讨,并将结果同24例正常人小腿皮肤及鼻孔的菌群做了比较。其结果表明:金黄色葡萄球菌为皮损及邻近皮肤的主要菌种,并且其分离率及密度有按正常皮肤、邻近皮肤、皮损依次增高现象;类白喉杆菌的数量在皮损部位明显低于正常皮肤与邻近皮肤;表皮葡萄球菌分离率皮损及邻近皮肤均明显降低。本组结果同正常对照组相比其皮肤微生物群菌谱虽无不同,但其数量的变异是显著的,这对探讨湿疹的病因及用生态制剂等调整皮肤菌群使其恢复微生态平衡达到防治目的有所裨益。     

Effect of radiation on skin expansion and skin flap viability in pigs

The aim of the present study was to investigate the effect of radiation treatment both on skin tissue expansion with the chronic inflation of subcutaneous expanders and on skin flap viability in surgically delayed and expanded skin in the pig. One flank in each of six pigs (initially weighing 17 +/- 1.8 kg) was randomly assigned for radiation treatment, and the contralateral flank served as a nonirradiated control. Three mirror-image, 8 x 10 cm, rectangular templates were marked on each flank; these templates were randomly assigned to the construction of a delayed skin flap (group A), a skin flap raised on expanded skin (group B), or a skin flap raised on expanded skin with a capsulectomy before flap surgery (group C). Radiation treatment was performed using sequential radiation with three fractions per week (810 cGy/fraction) for 2 weeks, with a total dose of 4,860 cGy. Twelve weeks after radiation treatment, skin expanders (8 x 10 cm) were installed subcutaneously in the locations assigned for skin expansion. Skin expansion by the inflation of subcutaneous skin expanders with saline twice weekly was started 8 weeks later and lasted for 3 weeks. Two weeks after surgical delay and the last skin expansion, 8 x 20 cm skin flaps were raised on the locations assigned for delayed skin flaps, expanded skin flaps, and expanded skin flaps with a capsulectomy. Skin flap viability was assessed 24 hours later using a fluorescein dye-staining technique. Skin expansion by the inflation of subcutaneous expanders with saline was slower (p < 0.05) in the radiated skin (39 +/- 6 ml/filling) than in the nonirradiated control skin (51 +/- 6 ml/filling). Radiation reduced the overall area of expanded skin by 23 percent (p < 0.05) compared with the control. Radiation treatment also reduced skin viability by 36 percent (p < 0.05) in the delayed skin flaps, 27 percent (p = 0.10) in the expanded skin flaps, and 36 percent (p < 0.05) in the expanded skin flaps with a capsulectomy when compared with their contralateral, nonirradiated controls. There were no significant differences in skin viability among these three types of skin flaps within the radiated and nonirradiated groups. Taken together, these observations indicate that radiation treatment reduced the effectiveness of the surgical delay procedure, the amount of subcutaneous skin expansion (by an increase in skin area), and skin flap viability. However, a capsulectomy alone did not affect the viability of skin flaps raised on expanded skin.     

Oxygenation and microcirculation during skin stretching in undermined and nonundermined skin

The aim of this experimental study was to assess the skin microcirculation of undermined and nonundermined wound edges closed with a skin-stretching device. In eight piglets, 9 x 9-cm wounds were created on both flanks by excision of the skin and the subcutaneous layer down to the muscular fascia, with general anesthesia. On one flank, the surrounding skin was completely undermined. For a period of 30 minutes, wound closure was performed with a stretching device, using the principle of load cycling. The device stretched the skin and moved the opposing wound edges toward each other. During this period, laser Doppler flowmetry and transcutaneous oximetry were simultaneously used to monitor microcirculation and oxygenation in the stretched skin of both flanks. Undermining of the surrounding skin produced a 12 percent decrease in the laser Doppler flowmetry signal and a 21 percent decrease in the transcutaneous oximetry value. Skin stretching resulted in decreases in the laser Doppler flowmetry signals and the transcutaneous oximetry values, whether or not the skin was undermined. Releasing the stretching device resulted in rapid normalization of the laser Doppler flowmetry values in undermined and nonundermined skin and a slow return of the transcutaneous oximetry values to close to baseline levels in nonundermined skin. The transcutaneous oximetry values in undermined skin did not return to baseline levels; each period of skin stretching resulted in an additional decrease in the transcutaneous oximetry values. Stretching of undermined skin for 30 minutes produced a significant (p < 0.0001) decrease in skin oxygenation. As a result, 50 percent of the undermined stretched skin demonstrated skin necrosis at the wound edges, which was still present after 1 week. Wound healing in the nonundermined stretched skin proceeded without problems. It is concluded from these experiments that the viability of undermined skin becomes compromised as a result of significantly decreased oxygen availability in the skin during and after stretching. Consequently, it is recommended that skin stretching be performed on nonundermined skin, rather than undermined skin. In addition, when skin is stretched to close a large defect, it is logical to use cyclic loading, so that recuperation of the skin circulation can occur. Furthermore, laser Doppler flowmetry seemed to produce atypical signals in monitoring of skin viability of wound edges closed with a skin-stretching device.     

Insulin receptor substrate 1 (IRS-1) plays a unique role in normal epidermal physiology

Insulin receptor substrate (IRS) proteins play a central role in insulin signaling. Previously we have demonstrated that insulin is essential for normal skin development and function. In the present study we investigated the involvement of the IRS-1 and IRS-2 proteins in skin physiology and in mediating insulin action in skin. For this purpose we have investigated the effects of inactivation of each of the IRSs on skin, studying skin sections and primary skin cells derived from IRS-1 or IRS-2 null mice. We have demonstrated that while the skin of the IRS-2 null mice appeared normal, the skin of the IRS-1 null mice was thinner and translucent. Histological analysis revealed that the thinning of the IRS-1 null skin was a consequence of the thinning of the spinous compartment, consisting of fewer layers. Proliferation of the IRS-1 and IRS-2 null skin epidermal cells was normal. However, the differentiation process of the IRS-1 skin and skin cells was impaired. There was a marked decrease in the induction of the expression of K1, the marker of advanced stages of skin differentiation. In contrary, IRS-2 inactivation had no effects on skin differentiation. In conclusion, we have shown for the first time that IRS-1 but not IRS-2 has an effect on skin formation and development, being one of the main activators of the differentiation process in skin keratinocytes. Furthermore, we suggest that IRS-1 and IRS-2 have distinct roles in skin physiology.     

后生元在皮肤健康与美容领域的开发与应用

后生元因为具有益生菌的某些功效,但又无活菌体,更易被商品化,且分子更小,更易被皮肤吸收,一直受到美容护肤领域的关注。影响皮肤老化的因素很多,皮肤微生态平衡是维持皮肤健康的必要因素。皮肤在病理状态会出现微生态失衡,皮肤微生物组在老化过程中也会不断发生变化。本文介绍了皮肤微生物群和后生元制剂的制备,综述了后生元在皮肤稳态的维持和美容护肤领域的开发与应用,探讨了后生元发挥作用的可能机制,为后生元在皮肤美容与健康领域的进一步开发与应用提供一定的依据。

     

Differential responses of male and female red swordtails to chemical alarm cues

Male and female red swordtails Xiphophorus helleri exposed in the laboratory to swordtail skin extract, fathead minnow Pimephales promelas skin extract and distilled water, significantly decreased activity in response to conspecific skin extract compared to minnow skin extract or distilled water. Moreover, males and females responded differentially to conspecific skin extract. Males tended to occupy the top compartment of the tank, whereas females tended to occupy the bottom compartment and seek shelter more. In a second experiment swordtails reduced activity significantly more in response to swordtail skin extract compared to closely related guppy Poecilia reticulata skin extract, minnow skin extract or distilled water. Swordtails also reduced activity significantly more to guppy skin extract compared to minnow skin and distilled water. However, males and females did not respond differentially to guppy skin extract. This suggests that chemical alarm cues are partially conserved within the Poeciliidae, but the level of response is of lower intensity to heterospecific skin extracts.     

Comprehensive candidate gene study highlights UGT1A and BNC2 as new genes determining continuous skin color variation in Europeans

Natural variation in human skin pigmentation is primarily due to genetic causes rooted in recent evolutionary history. Genetic variants associated with human skin pigmentation confer risk of skin cancer and may provide useful information in forensic investigations. Almost all previous gene-mapping studies of human skin pigmentation were based on categorical skin color information known to oversimplify the continuous nature of human skin coloration. We digitally quantified skin color into hue and saturation dimensions for 5,860 Dutch Europeans based on high-resolution skin photographs. We then tested an extensive list of 14,185 single nucleotide polymorphisms in 281 candidate genes potentially involved in human skin pigmentation for association with quantitative skin color phenotypes. Confirmatory association was revealed for several known skin color genes including HERC2, MC1R, IRF4, TYR, OCA2, and ASIP. We identified two new skin color genes: genetic variants in UGT1A were significantly associated with hue and variants in BNC2 were significantly associated with saturation. Overall, digital quantification of human skin color allowed detecting new skin color genes. The variants identified in this study may also contribute to the risk of skin cancer. Our findings are also important for predicting skin color in forensic investigations.     

Skin preservation at 4 degrees C: a species comparison

There are numerous experimental studies in the literature regarding skin storage and preservation. These studies are difficult to interpret due to the variety of storage techniques utilized and the number of different animal species used as skin donors. This study utilized a single cold storage protocol to test the effect of species variation on skin graft viability. Donor skin was obtained from five animal species and human surgical panniculectomy specimens. The skin was stored in modified Roswell Park Memorial Institute (RPMI) 1640 tissue culture media at 4 degrees C. Stored skin was transplanted to surgically created defects on athymic (nude) mice after specific storage intervals. Ten days after transplantation, the grafts were examined by gross and microscopic techniques. The viability of mouse, rat, and dog skin was significantly different from human skin, while stored rabbit and pig skin were similar to human skin. These results demonstrate the difficulty of applying the data of skin storage studies from nonhuman species to clinical practice. The data indicate that rabbit and pig skin may be used in laboratory studies of skin preservation at 4 degrees C with a strong likelihood that the results may be of clinical relevance in predicting the behavior of human skin under similar storage conditions.     

Gas flux through human skin: effect of temperature, stripping, and inspired tension

The flux of He and O2 through intact adult human skin was measured at various inspired concentrations and skin temperatures. The skin surface was then stripped with cellophane tape to alter the diffusional conductance of the stratum corneum. He flux for stripped skin was used to estimate skin perfusion as a function of local temperature, and diffusional conductance for O2 was estimated from O2 flux and perfusion. The flux of He or O2 at constant skin temperature can be related to inspired concentration by a simple linear model. Increasing surface temperature in the range 33-43 degrees C produced a much larger increase in O2 flux than in He flux for intact skin. Skin stripping greatly increased skin O2 flux. Estimated skin conductance for O2 showed a more marked temperature dependence than estimated skin perfusion. The results suggest that raising skin temperature in the range 38-43 degrees C has only a modest effect on skin perfusion and that stratum corneum conductance may have a major role in the large increase of O2 flux with temperature.     

Comparison of skin permeability of drugs in mice and human cadaver skin

In vitro percutaneous absorption of four antihypertensive drugs were carried out across the mice and human cavader skin in order to compare their skin permeability. An interesting trend was noticed in these experiments. Poorly water soluble drug prazosin hydrochloride showed 13 times enhanced flux in the mice skin whereas the steady-state flux of the water soluble drug propranolol hydrochloride was almost same in both human cadaver and mice skin. The permeation rate of prazosin hydrochloride and propranolol hydrochloride through the human cadaver skin fluctuated widely over time, but in mice skin, distinct trends were noticed. The study indicates that the overall permeation rate in mice skin is higher than that in the cadaver skin and the meeting of the target-flux in mice skin does not guarantee its good permeability in human skin.     

益生菌对皮肤光老化的修复作用及其机制研究进展

皮肤是人体最大的器官,也是机体防御外界各种物理、化学及病原微生物侵害的重要组织.皮肤系统若出现老化,则导致其功能衰退、防御功能下降,危害机体健康.日常生活中,各类光照时刻侵害着我们的皮肤,加速其老化的速度.研究指出,光照尤其是日光中的紫外辐射可通过直接损伤DNA、产生活性氧、降解细胞外基质和诱发炎症等多种方式损伤皮肤细...     

Novel cyclosporin derivatives featuring enhanced skin penetration despite increased molecular weight

Topical cyclosporin A (CsA, 1) is not effective in the treatment of skin diseases, due to its low skin penetration. Following a prodrug strategy, a series of novel derivatives of 1 and of 2-[O-(2-hydroxyethyl)-d-Ser(8)]-CsA (SDZ IMM 125, 5) with potentially enhanced skin penetration properties were synthesized, in order to achieve higher levels of the active parent drugs in the skin. Permeation through skin and prodrug/drug levels in the skin were measured in vitro using rat and human skin. Introduction of a polar side chain, either in the form of a positively charged quaternary amine, a negatively charged phosphate or sulfate, or an amphiphilic phosphocholine moiety, generally increased permeability. Maximal increase in permeability through skin relative to CsA was up to 300-fold with rat skin, and up to 16-fold with human skin. Penetration into skin, as evaluated by measurement of prodrug/drug concentrations in the skin after 48 h, could be enhanced up to 14-fold (rat and human skin). Increases of permeation rates and skin concentrations showed no strict correlation. Using the phosphate 10 as prodrug, a 2.5-fold higher concentration of the active parent compound (5) could be achieved in rat skin as when administering 5 itself. The results demonstrate that in contrast with the '500 Dalton rule', which postulates poor skin penetration of molecules larger than 500 Da, high skin permeation can be achieved also with compounds of a molecular weight in the range between 1200 and 1600 Da. Results also indicate that in principle higher skin levels of active drug can be attained with a prodrug strategy in this class of compounds.     

Transplantation and cellular reactions to tissue antigens in Streptococcus-immunized rabbits]

The immunization of rabbits with the cells and the disintegration products of fractions of the cytoplasmic membranes of group A streptococcus (type 1) in incomplete Freund adjuvant, introduced in a single injection into the pads of the paws, caused lesions in autoplastic skin grafts and accelerated the rejection of alloplastic skin grafts. The rabbits showed positive delayed-type skin reactions to streptococcus and homologous skin antigens, and lymphocytes specifically reacting with FITC-labeled homologous skin antigen were found in their blood. Prolonged intravenous immunization with streptococcus, which induced the formation of complement fixing antibodies to homologous skin antigens, did not influence the taking of autoplastic and alloplastic skin grafts. The injection of hyperimmune streptococcus rabbit antiserum containing antibodies to skin antigens to intact rabbits produced no lesions in the autoplastic skin grafts and prolonged the lift of the alloplastic skin grafts.     

新型持续皮肤牵张器促进皮肤创面愈合的实验研究

目的：介绍自主研制的持续皮肤牵张器,探讨自主研制的持续皮肤牵张器治疗皮肤缺损的可行性和效果分析。方法：自主研制的持续皮肤牵张器8套;白色家猪6只,将每只猪的背部（两侧）切除矩形皮肤软组织缺损,形成12个创面,分为二组,实验组4只猪8个创面,对照组2只猪4个创面,创面均为10cm×6cm,实验组创面用自制持续皮肤牵张器行皮肤伸展术治疗,对照组创面自行愈合。结果：实验组与对照组每日创面缩小面积相差较多,差异有统计学意义,实验组皮肤缺损行5-6天皮肤伸展术治疗后,可直接行二期缝合关闭,对照组1周后仍存在较大皮肤缺损,无法缝合关闭。结论：应用自制持续皮肤牵张器行皮肤伸展术,可以早期快速闭合皮肤创面。自制持续皮肤牵张器克服了以往牵张器的不足,具有使用方便,效果可靠,并发症少等优点,有良好的应用前景。     

Immunological challenges associated with artificial skin grafts: available solutions and stem cells in future design of synthetic skin

The repair or replacement of damaged skins is still an important, challenging public health problem. Immune acceptance and long-term survival of skin grafts represent the major problem to overcome in grafting given that in most situations autografts cannot be used. The emergence of artificial skin substitutes provides alternative treatment with the capacity to reduce the dependency on the increasing demand of cadaver skin grafts. Over the years, considerable research efforts have focused on strategies for skin repair or permanent skin graft transplantations. Available skin substitutes include pre- or post-transplantation treatments of donor cells, stem cell-based therapies, and skin equivalents composed of bio-engineered acellular or cellular skin substitutes. However, skin substitutes are still prone to immunological rejection, and as such, there is currently no skin substitute available to overcome this phenomenon. This review focuses on the mechanisms of skin rejection and tolerance induction and outlines in detail current available strategies and alternatives that may allow achieving full-thickness skin replacement and repair.     

Tension decrease during skin stretching in undermined versus not undermined skin: an experimental study in piglets

In a controlled study using 15 piglets, the efficacy of skin stretching using a skin stretching device was tested by quantifying the tension decrease during skin stretching in undermined and not undermined wounds. The viability of the skin margins was examined in both situations. Thirty standardized wounds was created: around 15 wounds on one flank, the surrounding skin was undermined; whereas around the 15 wounds on the opposite flank, the surrounding skin was not undermined. The force required to close the 9 x 9 cm defect was measured at the beginning, after undermining, and after 30 minutes of skin stretching. Also examined was the wound healing after 1 day and 1 week. A tension decrease of 3.02 N (13.6 percent reduction of the total force that is required to close the wound at the beginning) was seen due to undermining the surrounding skin. Skin stretching for 30 minutes without undermining the skin showed a tension decrease of 6.10 N (26.5 percent). Therefore, the tension decrease due to skin stretching was twice as high in comparison with undermining the skin margins alone. This has been statistically proven to be significant (-d (difference) = 3.08, 95 percent confidence interval = 2.16; 4.00, p < 0.001). When the undermined skin of the wound was stretched for 30 minutes, we measured a total tension decrease of 7.60 N (34.1 percent). There was a statistically significant but small difference in total tension decrease as a result of undermining combined with skin stretching in comparison with skin stretching without undermining (-d = 1.51, 95 percent confidence interval = 0.77; 2.23, p < 0.001). Undermining the surrounding skin involved cutting musculocutaneous perforating vessels. Looking at the viability of the skin, seven wounds, all found in the undermined group, showed skin necrosis after 1 week. Excessive seroma formation was seen in all wounds around which the skin was undermined. In the not undermined wounds, there were no problems in wound healing. In conclusion, skin stretching for only 30 minutes using a skin stretching device significantly reduces wound closing tension. The additional advantage of skin stretching over that of undermining alone is clearly shown. Undermining the wound margins before skin stretching gives a small additional tension decrease but has well-known complications, such as skin-edge necrosis and seroma formation.     

Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets for skin photoprotection.

Endogenous chromophores in human skin serve as photosensitizers involved in skin photocarcinogenesis and photoaging. Absorption of solar photons, particularly in the UVA region, induces the formation of photoexcited states of skin photosensitizers with subsequent generation of reactive oxygen species (ROS), organic free radicals and other toxic photoproducts that mediate skin photooxidative stress. The complexity of endogenous skin photosensitizers with regard to molecular structure, pathways of formation, mechanisms of action, and the diversity of relevant skin targets has hampered progress in this area of photobiology and most likely contributed to an underestimation of the importance of endogenous sensitizers in skin photodamage. Recently, UVA-fluorophores in extracellular matrix proteins formed posttranslationally as a consequence of enzymatic maturation or spontaneous chemical damage during chronological and actinic aging have been identified as an abundant source of light-driven ROS formation in skin upstream of photooxidative cellular stress. Importantly, sensitized skin cell photodamage by this bystander mechanism occurs after photoexcitation of sensitizers contained in skin structural proteins without direct cellular photon absorption thereby enhancing the potency and range of phototoxic UVA action in deeper layers of skin. The causative role of photoexcited states in skin photodamage suggests that direct molecular antagonism of photosensitization reactions using physical quenchers of photoexcited states offers a novel chemopreventive opportunity for skin photoprotection.     

Long-term survival of human skin allografts in patients with immunosuppression

Severe burn patients lack adequate skin donor sites to resurface their burn wounds. Patients with severe burn injuries to areas such as an entire face are presently reconstructed with skin grafts that are inferior to normal facial skin. This study was designed in part to determine whether human skin allografts would survive, repopulate, and persist on patients with immunosuppression and after discontinuation of immunosuppression. Small split-thickness skin grafts were synchronously transplanted at the time of renal transplantation from six renal transplant donors to recipients. All six patients were immunosuppressed with the usual doses of renal transplant immunosuppressants (methylprednisolone, cyclosporine, prednisone, and azathioprine). The skin allografts were biopsied when rejection was suspected and at various intervals. Special histologic studies were performed on skin biopsy specimens. Class II DNA tissue typing was performed on transplanted and autogenous skin biopsy specimens of four patients. Fluorescent in situ hybridization was performed successfully on skin biopsies of four patients' transplanted skin and on two of these four patients' autogenous skin. All six human skin allografts sustained a 100 percent take and long-term clinical survival. DNA tissue typing performed on skin allograft biopsy specimens from patients taking immunosuppressants all revealed donor and recipient cells. DNA tissue typing performed on autogenous skin biopsies from the same patients all revealed only recipient cells. Fluorescent in situ hybridization performed on allograft and autogenous specimens from patients taking immunosuppressants revealed transplanted donor cells with rare recipient cells in the allograft and only recipient cells in the autogenous skin. This study of six patients proves that it is possible for human skin allografts to survive indefinitely on patients taking the usual dosages of immunosuppressants used for renal transplantation. There was minimal repopulation of skin allografts by autogenous keratinocytes and fibroblast while patients were taking immunosuppressants. Immunosuppression was discontinued in two patients after renal transplant rejection after 6 weeks and 5 years. When immunosuppression was discontinued after 5 years in one patient, the skin allograft cells were destroyed and replaced with autogenous cells, but the skin graft did not reject acutely and persisted clinically. It is hypothesized that the acellular portion of the skin allograft was not rejected acutely because of relatively low antigenicity and because it acted as a lattice for autogenous cells to migrate into and replace rejected allograft skin cells. No chimerism was seen in autogenous skin in the skin-renal transplant patients in this study.