Hairless Mice Research Articles

Protective effects of red orange (Citrus sinensis [L.] Osbeck [Rutaceae]) extract against UVA-B radiation-induced photoaging in Skh:HR-2 mice.

The skin is the outermost organ of the human body and plays a protective role against external environmental damages, such as sunlight and pollution, which affect anti-oxidant defenses and skin inflammation, resulting in erythema or skin reddening, immunosuppression, and epidermal DNA damage. The present study aimed to investigate the potential protective effects of red orange complex H extract (ROC) against ultraviolet (UV)-induced skin photoaging in Skh:HR-2 mice. ROC was orally administered at doses of 20, 40, and 80 mg/kg/day for 13 weeks, along with UV irradiation of the mice for 10 weeks. ROC improved UV-induced skin barrier parameters, including erythema, melanin production, transepidermal water loss, elasticity, and wrinkle formation. Notably, ROC inhibited the mRNA expression of pro-inflammatory cytokines (interleukin 6 and tumor necrosis factor α) and melanogenesis. In addition, ROC recovered the UV-induced decrease in the hyaluronic acid and collagen levels by enhancing genes expression. Furthermore, ROC significantly downregulated the protein and mRNA expression of matrix metalloproteinases responsible for collagen degradation. These protective effects of ROC against photoaging are associated with the suppression of UV-induced phosphorylation of c-Jun NH2-terminal kinase and activator protein 1 activation. Altogether, our findings suggest that the oral administration of ROC exerts potential protective activities against photoaging in UV-irradiated hairless mice.

Fish Collagen Peptide (NaticolⓇ) Protects the Skin from Dryness, Wrinkle Formation, and Melanogenesis Both In Vitro and In Vivo.

Consistent ultraviolet B (UVB) radiation exposure results in dry skin, wrinkles, and melanogenesis. In this study, we investigated whether fish collagen peptide (NaticolⓇ) could inhibit photoaging and oxidative stress in skin exposed to UVB using cell and animal models. We measured the skin hydration, histological observations, antioxidant activities, moisturizing-related factors, collagen synthesis-related factors, and melanogenesis-related factors in skin cells and animal skin using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blot assay. NaticolⓇ collagen improved skin moisturization via hyaluronic acid and ceramide synthesis-related factors in HaCaT cells and SHK-I hairless mice that were exposed to UVB. In addition, NaticolⓇ collagen inhibited wrinkle formation in Hs27 cells and SHK-I hairless mice exposed to UVB and restrained melanogenesis in 3-isobutyl-1-methylxanthine-induced B16F10 cells and UVB-irradiated SHK-I hairless mice. On the basis of these findings, we propose that ingestion of Naticol Ⓡ collagen might be valuable for preventing skin photoaging.

Dieckol Isolated from Eisenia bicyclis Ameliorates Wrinkling and Improves Skin Hydration via MAPK/AP-1 and TGF-β/Smad Signaling Pathways in UVB-Irradiated Hairless Mice.

Repetitive exposure to ultraviolet B (UVB) is one of the main causes of skin photoaging. We previously reported that dieckol isolated from Eisenia bicyclis extract has potential anti-photoaging effects in UVB-irradiated Hs68 cells. Here, we aimed to evaluate the anti-photoaging activity of dieckol in a UVB-irradiated hairless mouse model. In this study, hairless mice were exposed to UVB for eight weeks. At the same time, dieckol at two doses (5 or 10 mg/kg) was administered orally three times a week. We found that dieckol suppressed UVB-induced collagen degradation and matrix metalloproteinases (MMPs)-1, -3, and -9 expression by regulating transforming growth factor beta (TGF-β)/Smad2/3 and mitogen-activated protein kinases (MAPKs)/activator protein-1 (AP-1) signaling. In addition, dieckol rescued the production of hyaluronic acid (HA) and effectively restored the mRNA expression of hyaluronan synthase (HAS)-1/-2 and hyaluronidase (HYAL)-1/-2 in UVB-irradiated hairless mice. We observed a significant reduction in transepidermal water loss (TEWL), epidermal/dermal thickness, and wrinkle formation in hairless mice administered dieckol. Based on these results, we suggest that dieckol, due to its anti-photoaging role, may be used as a nutricosmetic ingredient for improving skin health.

Combined Orobol-Bentonite Composite Formulation for Effective Topical Skin Targeted Therapy in Mouse Model.

Orobol is an isoflavone that has a potent skin protection effect. The objective of this study was to prepare a novel bentonite-based composite formulation of orobol to enhance topical skin delivery. The composition was optimized based on the orobol content in the composite and the in vitro release studies, followed by the in vitro and in vivo hairless mouse skin deposition studies. Physicochemical characterizations of the composite formulation were performed by powder X-ray refractometry (XRD) and scanning electron microscopy (SEM). The in vitro cytotoxicity and in vivo toxicity studies were conducted in human keratinocytes and in hairless mouse, respectively. The in vitro release of orobol from the bentonite composites was higher than that from the suspension, which was further increased with the addition of phosphatidylcholine. The composite formulation significantly enhanced the in vitro and in vivo skin deposition of orobol in hairless mouse skin compared to the orobol suspension. Moreover, the addition of phosphatidyl choline not only improved the dissolution and incomplete release of orobol from the bentonite composite but also enhanced the deposition of orobol in the skin. XRD histograms and SEM images confirmed that the enhanced dissolution of orobol from the composite was attributed to its amorphous state on bentonite. The in vitro and in vivo toxicity studies support the safety and biocompatibility of the orobol-loaded bentonite composite formulation. These findings suggest that the orobol-loaded bentonite composite formulation could be a potential topical skin delivery system for orobol.

Protective Effect of Bifidobacterium animalis subs. lactis MG741 as Probiotics against UVB-Exposed Fibroblasts and Hairless Mice.

Skin photoaging, which causes wrinkles, increased epidermal thickness, and rough skin texture, is induced by ultraviolet B (UVB) exposure. These symptoms by skin photoaging have been reported to be involved in the reduction of collagen by the expression of matrix metalloproteinases (MMPs) and activator protein-1 (AP-1). This study investigated the protective effects of Bifidobacterium animalis subsp. lactis MG741 (Bi. lactis MG741) in Hs-68 fibroblasts and hairless mice (HR-1) following UVB exposure. We demonstrated that the Bi. lactis MG741 reduces wrinkles and skin thickness by downregulating MMP-1 and MMP-3, phosphorylation of extracellular signal-regulated kinase (ERK), and c-FOS in fibroblasts and HR-1. Additionally, in UVB-irradiated dorsal skin of HR-1, Bi. lactis MG741 inhibits the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), an inflammation-related factor. Thus, Bi. lactis MG741 has the potential to prevent wrinkles and skin inflammation by modulating skin photoaging markers.

Does systemic hydrochlorothiazide increase the risk of developing ultraviolet radiation-induced skin tumours in hairless mice?

Hydrochlorothiazide (HCTZ) is a frequently prescribed diuretic that exhibits photosensitizing properties. It is used to treat hypertension and edema. Dermato-epidemiological studies in various populations have linked HCTZ treatment with increased risk of particular types of skin cancer, including malignant melanoma (lentigo subtype), and both basal cell carcinoma and squamous cell carcinoma (SCC). This study investigated whether either of two different doses of HCTZ increased the risk of SCC development in mice exposed to ultraviolet radiation (UVR). A total of three groups of hairless mice were used in this study (total, N= 71). One group received a low dose (0.26 mg/mouse/day) and another group received a high dose (0.52 mg/mouse/day) of HCTZ in their drinking water; a third UVR control group received only tap water. All three groups were irradiated with UVR until the mice developed three tumours that were 4 mm in size. The times to SCC tumour development were recorded. In the low-dose group, the median time to develop an SCC tumour was 170 days; in both the high-dose group and the control group, the median time to develop anexd SCC tumour was 163 days (p≥ 0.331). In our hairless mouse model, we found that mice treated with UVR plus HCTZ did not develop SCCs more rapidly than mice treated with UVR but not HCTZ.

Comparison of global DNA methylation analysis by whole genome bisulfite sequencing and the Infinium Mouse Methylation BeadChip using fresh and fresh-frozen mouse epidermis

ABSTRACT Until recently, studying the murine methylome was restricted to sequencing-based methods. In this study we compared the global DNA methylation levels of hairless mouse epidermis using the recently released Infinium Mouse Methylation BeadChip from Illumina and whole genome bisulphite sequencing (WGBS). We also studied the effect of sample storage conditions by using fresh and fresh-frozen epidermis. The DNA methylation levels of 123,851 CpG sites covered by both the BeadChip and WGBS were compared. DNA methylation levels obtained with WGBS and the BeadChip were strongly correlated (Pearson correlation r = 0.984). We applied a threshold of 15 reads for the WGBS methylation analysis. Even at a threshold of 10 reads, we observed no substantial difference in DNA methylation levels compared with that obtained with the BeadChip. The DNA methylation levels from the fresh and the fresh-frozen samples were strongly correlated when analysed with both the BeadChip (r = 0.999) and WGBS (r = 0.994). We conclude that the two methods of analysis generally work equally well for studies of DNA methylation of mouse epidermis and find that fresh and fresh-frozen epidermis can generally be used equally well. The choice of method will depend on the specific study’s aims and the available resources in the laboratory.

Light-Touch-Induced Afterdischarge Firing in the Superficial Spinal Dorsal Horn Neurons in Hairless Mice with Irritant Contact Dermatitis.

The skin is an important barrier that protects against invasion by foreign substances, including irritants and harmful microorganisms, and holds water in the body. Washing the skin with cleansers and shampoos containing anionic surfactants, for example sodium dodecyl sulfate (SDS), is important for maintaining skin homeostasis. However, surfactants can cause dermatitis, cutaneous hypersensitivity (e.g., alloknesis), and pruritus in humans. Our previous studies revealed an alloknesis response in the skin with SDS-induced dermatitis in C57BL/6 mice. In addition, we found that alloknesis responses and afterdischarge responses following stimulation with light touch are related because they are observed contemporaneously. In this study, we used Hos:HR-1 hairless mice to establish a mouse model to evaluate long-term drug application for alloknesis responses. Alloknesis was observed in HR-1 mice with SDS-induced dermatitis. The mean number of c-Fos (a marker of neural activity) immunopositive neurons was increased in the lamina 1-2 (L1-2) spinal dorsal horn, but not in L3-4, of SDS-treated HR-1 mice compared to vehicle-treated mice. We also discovered that afterdischarge responses were observed in neurons in L1-2. There was also a correlation between the intensity of the afterdischarge responses and depth of the recording site. Thus, the following were suggested: 1) neurons that mediate these afterdischarge responses are located on the superficial layer of the spinal cord; 2) afterdischarge responses can be an index of alloknesis responses, and 3) the mouse model of SDS-induced dermatitis is an appropriate alloknesis model.

Enzyme-Treated Caviar Prevents UVB Irradiation-Induced Skin Photoaging.

For this research article, we investigated the protective effects of enzyme-treated caviar powder extract (CV) in ultraviolet B (UVB)-irradiated hairless mice and keratinocytes by confirming moisturizing-related factors and elasticity-related factors. UVB irradiation induced wrinkle formation, dehydration, oxidative stress, and inflammation in the dorsal skin of mice; however, these were suppressed in the CV-supplemented groups in UVB-irradiated hairless mice. Furthermore, in UVB-irradiated keratinocytes, CV treatment increased the antioxidant enzyme activities and the levels of sphingomyelin and hyaluronic acid and decreased the production of pro-inflammatory cytokines and the expression of IkB-α and p65 phosphorylation. These findings indicate that CV can directly protect keratinocytes against UVB irradiation-induced oxidative stress and inflammation. Therefore, we suggest that CV can protect against UVB-induced skin photoaging. Therefore, we suggest that caviar is effective for skin health by preventing UVB-induced skin photoaging.

Anti-skin aging activity of eggshell membrane administration and its underlying mechanism

BackgroundThere is active research on developing materials for improving skin function. Eggshell membrane (ESM) is one such raw material that is consumed as a functional food to support skin health. However, studies on the mechanism of improvement of skin function on ingestion of ESM are still lacking.ObjectivesTo explore this mechanism of action, we conducted an ultraviolet (UV) irradiation study on a SKH-1 hairless mouse model. Feeding ESM was found to improve skin moisture and reduce wrinkles during 12 weeks of UVB irradiation.ResultsOral administration of ESM restored moisture in the dorsal skin tissue of mice. In addition, oral ingestion of ESM also reversed the increased transepidermal water loss and reduction of mRNA expression of hyaluronic synthases induced by UVB irradiation. Furthermore, UVB irradiation-induced collagen degradation was inhibited, and the expression of the collagenase MMP was reduced in the ESM intake group compared to the control. These results confirmed that oral ingestion of the ESM has an anti-wrinkle effect. In addition, the mRNA expression of the antioxidant enzyme SOD1, which was reduced on UVB irradiation, was restored on ingestion of the ESM. Restoring the expression of antioxidant enzymes is a key strategy for improving skin function of the ESM.ConclusionTaken together, the findings from our study reveal the potential of ESM as a nutricosmetic material with anti-wrinkle and skin moisturizing properties.

Development of a Novel IgG1 Anaphylaxis Mouse Model with Uniquely Characteristic Skin Manifestations Induced Through the FcγRIII-Histamine Pathway

ABSTRACT Background Studies of passive anaphylaxis, in which mouse immunoglobulin G (IgG) and its antigens are administered to mice, believe that platelet-activating factor (PAF) is more important than histamine and that basophils or macrophages are primarily involved. However, the full extent of IgG-dependent anaphylaxis is still unclear; that is, little agreement has been reached about the mechanism. Methods First, we established the novel model of IgG1 anaphylaxis induced by the intravenous administration of two types of IgG1 and a fluorescent dye-labeled antigen, as IgG1 immune complex in HR-1 hairless mice. Subsequently, pharmacological analysis was used to investigate the underlying mechanisms of IgG1 anaphylaxis in this established model. Results The novel IgG1 anaphylaxis model can induce the IgG-induced Anaphylaxis-dependent Spotted Distribution of fluorescently labeled Immune complexes in the Skin, named “G-ASDIS”. Moreover, this model was triggered primarily by the FcγRIII-dependent histamine release, which is different from the conventional model in which PAF was involved in the development of IgG1 anaphylaxis. Basophils in the circulation and mast cells in the skin may participate in the development of IgG1 anaphylaxis and increased G-ASDIS. Conclusion Our results propose that the novel axis, namely the FcγRIII-basophils and/or mast cell-histamine pathway, is important for IgG1 anaphylaxis. Further analysis of our model in addition to other models will lead to a broader analysis and understanding of the IgG1 anaphylaxis mechanism.

Nanodroplets for methicillin-resistant Staphylococcus aureus (MRSA) eradication in murine diabetic wounds

Bacterial biofilms are the leading cause of delayed healing in chronic wounds. Aminoglycoside antibiotics, such as gentamicin (Gent), are ineffective against biofilm cells as they maintain proton motive force below the threshold for drug uptake. We employ a novel aminoglycoside adjuvant, palmitoleic acid (PA), to facilitate drug uptake. Here, we propose a dual strategy to eradicate a chronic wound infection; utilizing ultrasound-stimulated nanodroplets (US+ND) to improve the penetration of the novel drug combination Gent/PA. A chronic wound infection model was established in SKH-1 hairless mice; 6–8 week old mice were treated with streptozocin to induce diabetes. A circular wound was created on the back of the mice and infected with methicillin-resistant Staphylococcus aureus (MRSA). Wounds were treated topically with Gent and/or PA, twice daily for four days. One daily antibiotic treatment was combined with US+ND. On day 5, mice were euthanized and the wound area was excised and plated to enumerate bacterial survivors. Neither Gent nor Gent/PA reduced bacterial burden but both treatments were significantly improved by applying US+ND to improve drug penetration. Importantly, bacteria were eradiated from 3 out of the 8 wounds in the Gent/PA group that were treated with US+ND. These data show that improving the penetration of a novel anti-biofilm drug combination is a viable strategy to eradicate biofilms in chronic wounds. [Some authors are inventors on patents related to this work.]

Construction of a Secondary Enclosure for UVB Irradiation of Mice

UV irradiation is commonly used in murine models of skin cancers. Despite the popularity of using UVB rays to model photocarcinogenesis in animals, there is a lack of standardization in the secondary enclosures used to administer radiation. An appraisal of the literature also shows a general lack of details regarding the materials and procedures utilized in the fabrication of such enclosures. We present in this study a detailed overview of the construction of a UVB exposure chamber that successfully induces lesions in hairless mice. A standardized protocol for producing a UVB enclosure may reduce methodological variation in future studies seeking to investigate photocarcinogenesis in animals.

Protective Effects of Orange Sweet Pepper Juices Prepared by High-Speed Blender and Low-Speed Masticating Juicer against UVB-induced Skin Damage in SKH-1 Hairless Mice.

Sweet pepper fruits (Capsicum annuum L.) contain various nutrients and phytochemicals that enhance human health and prevent the pathogenesis of certain diseases. Here, we report that oral administration of orange sweet pepper juices prepared by a high-speed blender and low-speed masticating juicer reduces UVB-induced skin damage in SKH-1 hairless mice. Sweet pepper juices reduced UVB-induced skin photoaging by the regulation of genes involved in dermal matrix production and maintenance such as collagen type I α 1 and matrix metalloproteinase-2, 3, 9. Administration of sweet pepper juices also restored total collagen levels in UVB-exposed mice. In addition, sweet pepper juices downregulated the expression of pro-inflammatory proteins such as cyclooxygenase-2, interleukin (IL)-1β, IL-17, and IL-23, which was likely via inhibiting the NF-κB pathway. Moreover, primary antioxidant enzymes in the skin were enhanced by oral supplementation of sweet pepper juices, as evidenced by increased expression of catalase, glutathione peroxidase, and superoxide dismutase-2. Immunohistochemical staining showed that sweet pepper juices reduced UVB-induced DNA damage by preventing 8-OHdG formation. These results suggest that sweet pepper juices may offer a protective effect against photoaging by inhibiting the breakdown of dermal matrix, inflammatory response, and DNA damage as well as enhancing antioxidant defense, which leads to an overall reduction in skin damage.

Effect of standard skin care treatments on skin barrier function in X-irradiated hairless mice

ObjectiveThe effectiveness of skin care to radiation dermatitis (RD) on patients who received radiotherapy for cancer has not been clarified. The purpose of this study was to investigate the effect of moisturizers and skin washing on skin barrier function possibly leading to the development of RD using X-ray irradiated hairless mice. MethodsNine-week-old hairless mice were irradiated with 10 ​Gy of X-rays, and the skin care group had moisturizers applied or skin washing with soap from the day of irradiation during observations. The condition of the skin was observed to evaluate RD. Skin barrier function was evaluated by measuring skin temperature and transepidermal water loss (TEWL) once every two days until 25 days after X-ray irradiation. ResultsRD was not observed in all groups until 25 days after X-ray irradiation. Skin temperature tended to increase in all groups regardless of irradiation or skin care. However, unlike the control group, the measured value of TEWL in the no skin care group tended to increase in the days after the X-ray irradiation. On the other hand, TEWL was increased in the skin care group compared with the no skin care group a few days after X-ray irradiation. While TEWL was constant in the moisturizer group, the skin washing groups showed an increasing tendency of TEWL and it reached a peak at 13 days after X-ray irradiation. ConclusionsThese results suggested that the decrease in skin barrier function was caused by X-ray irradiation and also that skin washing could contribute to the deterioration of skin barrier function after X-ray irradiation.

Glucocerebroside-Containing Milk Concentrated Powder Suppresses Oxidative Stress and Photoaging in the Skin of Hairless Mice.

This study investigated the protective effects of glucocerebroside-containing buttermilk concentrated powder (GCBM) on oxidative stress and photoaging in ultraviolet B (UVB)-irradiated hairless mice. We measured antioxidant enzyme activities, collagen synthesis-related pathways, and moisturizing-related factors in the dorsal skin of mice. We observed that dietary supplementation with GCBM increased antioxidant enzyme activity and decreased pro-inflammatory cytokine expression in the UVB-irradiated dorsal skin. Furthermore, dietary supplementation with GCBM inhibited wrinkle formation by suppressing the JNK/c-FOS/c-Jun/MMP pathway and stimulating the TGF-βRI/Smad3/procollagen type I pathway. Dietary supplementation with GCBM also increased skin moisturization by stimulating hyaluronic acid and ceramide synthesis in the dorsal skin. Therefore, buttermilk powder supplementation helps prevent photoaging and can be used as an effective component in developing anti-photoaging products.

Human activity-driven self-powered hair follicle stimulation system

Alopecia is one of the most common and distressing diseases that can remain traumatic for an individual. Various pharmacological and non-pharmacological treatments for alopecia have been developed; however, critical side effects (e.g., impotence) or limitations in terms of hair regeneration potential still exists. One of the non-pharmacological treatments, physical stimulation, has been proven effective for hair regeneration; however, the resultant discomfort and the need for external components such as power supply remain problems in its widespread use. Here, we introduce an innovative human activity-driven internal hair follicle stimulation system (HIFS) that utilizes alternating current (AC) electric energy abandoned during human activities to internally stimulate hair follicles and tissues through the human body. The internal electric field concentration by simply applying conductive gel HIFS and cap-type/hairpin-type HIFS was investigated via 3D electrostatic simulation and actual electrical measurement experiments. The internally concentrated electric field could significantly increase the secretion of hair regeneration-associated growth factors in the tissues and the number of hair follicles in hair-less mice without any side effects.

Alpinia officinarum Rhizome ameliorates the UVB induced photoaging through attenuating the phosphorylation of AKT and ERK

BackgroundChronic ultraviolet (UV) exposure is one of the major external factors in skin aging, and repetitive UVB exposure induces extracellular matrix (ECM) damage as well as metabolic disease. Alpinia officinarum Rhizome (AOR) is a medicinal plant that has been traditionally used for treating rheumatism and whooping cough. However, the antiphotoaging effects of AOR remain unclear. We investigated the protective effects of water extracts of AOR (WEAOR) in terms of UVB-mediated ECM damage, wrinkle formation, inflammatory responses, and intracellular signaling on hairless mice and NIH-3T3 skin fibroblast cells.MethodsWEAOR was administered to UVB-irradiated hairless mice. Wrinkle formation was assessed using the replica assay, epidermal changes through H&E staining, and collagen contents in mice skin through Masson’s trichrome staining. The expression of procollagen type-1 (COL1A1), metalloproteinase-1a (MMP-1a), and inflammatory cytokines (IL-6, IL-8, and MCP-3) in hairless mice skin and NIH-3T3 cells was investigated through qRT-PCR. The effects of WEAOR or signaling inhibitors on UVB-induced expression of intracellular mitogen-activated protein kinases (MAPKs) were estimated by Western blotting and qRT-PCR, respectively.ResultsTopical WEAOR significantly attenuated the UVB-induced wrinkle formation and epidermal thickening in the skin of hairless mice. WEAOR treatment also attenuated the UVB-induced expression of MMP-1a and COL1A1 and recovered the reduction of collagen content in mouse skin. These effects were confirmed in NIH-3T3 skin fibroblast cells. WEAOR treatment restored the UVB-induced COL1A1 and MMP-1a gene expression and attenuated the UVB-induced expression of IL-6, IL-8, and MCP-3 in NIH-3T3 cells. Notably, WEAOR attenuated UVB-induced phosphorylation of AKT and ERK, but not that of p38 and JNK in NIH-3T3 cells. In addition, the administration of AKT and ERK inhibitors restored the UVB-induced expression of MMP-1a and COL1A1 to an equal extent as WEAOR in NIH-3T3 cells.ConclusionsThe antiphotoaging properties of WEAOR were first evaluated in this study. Our results suggest that WEAOR may be a potential antiphotoaging agent that ameliorates UVB-induced photoaging processes via the AKT and ERK signaling pathways.

Comprehensive analysis reveals potential hub genes and therapeutic drugs in an acquired lymphedema model.

BackgroundAcquired lymphedema is a common and often severe complication of breast cancer surgery and radiology that seriously affects patients’ quality of life. Nevertheless, the pathogenesis for acquired lymphedema is complex and remains unclear. The aim of this study is to find out possible genetic markers and potential drugs for acquired lymphedema.MethodsFirst, the GSE4333 datasets, which include expression data for six female humanized hairless immunocompetent SKH-1 mice (the condition of whom mimics acquired lymphedema), were reanalyzed. According to the criteria of a fold change (FC) ≥1.4 and an adjusted P value <0.05, we identified the differentially expressed genes (DEGs) between a normal group and the lymphedema group. Next, we analyzed the Gene Ontology (GO) terms and enriched signaling pathways associated with these DEGs with an online tool DAVID. We also constructed protein-protein interaction (PPI) networks and selected meaningful gene modules for additional gene-drug interaction research. Finally, the extant drugs targeting these module genes were identified for further study of their therapeutic effects against acquired lymphedema.ResultsA total of 481 DEGs were identified that were closely associated with the immune system, inflammatory response, and extracellular matrix (ECM) structural constituent terms, among others. Moreover, we identified the top 10 significant genes in the PPI networks and identified one extant drug, fiboflapon, that targets the ALOX5AP gene.ConclusionsWe ultimately identified 10 hub genes, molecular mechanisms, and one extant drug related to acquired lymphedema. The findings identified targets and a potential drug for further research on acquired lymphedema.

Transdermal delivery of bFGF with sonophoresis facilitated by chitosan nanocarriers

The basic fibroblast growth factor (bFGF) is a potent angiogenic growth factor. Supplemental bFGF is essential for healing damaged skin, but its therapeutic use has been limited owing to its inherent instability. In this study, we propose a transdermal delivery system using sonophoresis along with the use of carboxymethyl chitosan nanocarriers which enables the administration of bFGF over a wide area of skin. The transdermal effect of the low-frequency ultrasound-enhanced delivery system was demonstrated in ex vivo experiments using hairless mouse skin. The subcutaneous administration of chitosan nanoparticles was evaluated by using fluorescence-labeled chitosan. To stably load bFGF into chitosan nanoparticles, a carrier with carboxymethyl chitosan was synthesized under a pH of around 7. Based on the results, we evaluated the effectiveness of transdermal drug delivery using sonophoresis. In skin cryosections, bFGF-loaded carboxymethyl chitosan nanocarriers delivered by ultrasound irradiation were present subcutaneously. We analyzed the bFGF content in skin tissue by ELISA and found that bFGF penetration in skin irradiated by ultrasound with nanocarriers. Penetration of bFGF-leaded carboxymethyl chitosan nanocarriers by ultrasound was significantly higher than that by ultrasound irradiation alone. Our results lay the groundwork for further utilization of polymeric nanocarriers using sonophoresis for the administration of biomacromolecules.