Shiou-Hwa Jee

• MD, PhD
• Medical Doctor at National Taiwan University

(1) Background: Human keratinocytes and murine skin express various cytochrome P450 enzymes. These include cytochrome P450 3A4, which may participate in the metabolism of cytochrome P450 3A4 substrate drugs. Desoximetasone, a topical corticosteroid and cytochrome P450 3A4 substrate, is used to treat skin conditions such as skin allergies, atopic de...

Skin barrier functions, environmental insults, and genetic backgrounds are intricately linked and form the basis of common inflammatory skin disorders, such as atopic dermatitis, psoriasis, and seborrheic dermatitis, which may seriously affect one’s quality of life. Topical therapy is usually the first line of management. It is believed that succes...

Psoriasis is a chronic, recurrent, immune-mediated disease involving the skin and joints. Epidermal hyperproliferation, abnormal keratinocyte differentiation, angiogenesis with blood vessel dilatation, and excess T helper type-1 (Th-1) and Th-17 cell infiltration are the main histopathological features of psoriasis. Magnolol is a polyphenolic compo...

Repigmentation of vitiligo relies on the proliferation and migration of melanoblasts from hair follicles to the epidermis to replenish epidermal melanin. Our previous study has demonstrated low‐intensity pulsed ultrasound (LIPUS) can stimulate melanoblast migration in vitro. We sought to evaluate the potential additive efficacy and safety of LIPUS...

Psoriasis is a chronic inflammatory skin disorder with a pathogenesis involving the interleukin-23/interleukin-17 axis. Salvianolic acid B exerts several pharmacological effects, such as antioxidation, anti-inflammation, and antitumor effects. The anti-psoriatic effects of salvianolic acid B have not been reported. In this study, we aimed to determ...

Melanin is known to provide strong third-harmonic generation (THG) contrast in human skin. With a high concentration in basal cell cytoplasm, THG contrast provided by melanin overshadows other THG sources in human skin studies. For better understanding of the THG signals in keratinocytes without the influence of melanin, an in vivo THG microscopy (...

Insulin-like growth factor-II mRNA-binding protein 3 (IMP-3) is an RNA-binding protein expressed in multiple cancers, including melanomas. However, the expression of IMP-3 has not been investigated in acral lentiginous melanoma (ALM). This study sought to elucidate its prognostic value in ALMs. IMP-3 expression was studied in 93 patients diagnosed...

Representative sections with immunohistochemical staining intensity against IMP-3. (A) IMP-3 staining was negative. (B) IMP-3 staining shows weak intensity. (C) IMP-3 staining shows moderate intensity. (D) IMP-3 staining shows strong intensity (Bar, 100 μm). (TIF)

Univariate and multivariate analysis of risk factors associated with overall survival (OS) in acral lentiginous melanoma patients. (DOCX)

Univariate and multivariate analysis of risk factors associated with recurrence-free survival (RFS) in acral lentiginous melanoma patients. (DOCX)

Univariate and multivariate analysis of risk factors associated with distant metastasis-free survival (DMFS) in acral lentiginous melanoma patients. (DOCX)

BRAF and NRAS mutations have been described in melanomas among Caucasians and some Asian populations. However, few large-scale studies have investigated the status and clinical significance of BRAF and NRAS mutations in a Taiwanese population. Melanoma samples (n = 119) were analyzed for mutations in exons 11 and 15 of the BRAF gene, and in exons 1...

Background and Objectives Hair follicles are located at the interface of the external and internal environments and their cycling has been shown to be regulated by intra- and extra-follicular factors. The aim of this study is to examine whether or how hair follicles respond to visible light.Study Design/Materials and Methods We examined the effect...

Insulin-like growth factor II mRNA-binding protein 3 (IMP-3) has been reported to be a novel marker of melanoma progression. However, the mechanisms by which it impacts melanoma are incompletely understood. In this study, we investigate the clinical significance of IMP-3 in melanoma progression and also its underlying mechanisms. We found that IMP-...

Background: Interleukin (IL)-31 induces severe pruritus and dermatitis in transgenic mice, and is associated with many itching skin diseases. Objective: We sought to investigate the association of serum IL-31 levels with uremic pruritus in patients undergoing hemodialysis. Methods: Patients receiving maintenance hemodialysis in a referral medi...

Uremic pruritus is a common and intractable symptom in patients on chronic hemodialysis, but factors associated with the severity of pruritus remain unclear. This study aimed to explore the associations of metabolic factors and dialysis adequacy with the aggravation of pruritus. We conducted a 5-year prospective cohort study on patients with mainte...

Background: Although pruritus is a common complaint in patients with diabetes, little is known about its relation with glycemic control. Objectives: We investigated whether generalized pruritus is associated with glycemic control in patients with type 2 diabetes. Materials and methods: A total of 385 patients with type 2 diabetes who attended...

Repigmentation of vitiliginous lesions relies on the proliferation and migration of melanoblasts from hair follicles to the epidermis. Pulsed ultrasound has been demonstrated to have stimulatory effects on cell proliferation and migration and has been applied clinically to enhance tissue repair. To clarify the biologic effects and signaling mechani...

Higher CXCR4 expression enhances basal cell carcinoma (BCC) invasion and angiogenesis. The underlying mechanism of increased CXCR4 expression in invasive BCC is still not well understood. To investigate the mechanisms involved in the regulation of CXCR4 expression in invasive BCC. We used qRT-PCR, RT-PCR, Western blot, and flow cytometric analyses...

To determine the efficacy of excimer light in the treatment vitiligo and to assess parameters affecting therapeutic results. This retrospective study analyzed 227 patches of vitiligo in 142 patients. Treatment was performed twice weekly and treatment efficacy was assessed by two independent dermatologists. Patients who received less than 24 treatme...

Tungiasis is a cutaneous parasitic infection caused by the sand flea Tunga penetrans. This infection is endemic to Central and South America, the Caribbean, and sub-Saharan Africa and is more prevalent in resource-poor communities. Increased air travel, emigration from, and immigration to these countries can lead to the import of T. penetrans to tr...

Continuous-wave (CW) laser-induced thermotherapy (LIT) can heat tumors to above 42ºC and lead to tumor destruction. During LIT, antibody-conjugated gold nanorods (AuNRs) can bind to tumor tissue and improve therapeutic efficacy when implementing plasmonic photothermal therapy (PPTT). This study uses a noninvasive photoacoustic (PA ) technique to mo...

Hypoxia-inducible factor-1alpha (HIF-1alpha) is widely considered to be one of the key regulators of tumor angiogenesis. The upstream regulation is complex and involves several growth factors, cytokines, and hypoxia. Herein, we have identified miR-519c as a hypoxia-independent regulator of HIF-1alpha, acting through direct binding to the HIF-1alpha...

A minimally invasive imaging modality that provides both cellular and extracellular structural information with subcellular resolution is helpful for clinical diagnosis as well as basic laboratory research in dermatology. Multiphoton microscopy (MPM), using femtosecond laser as the light source, is efficient in non-linear excitation of endogenous f...

Both reflected confocal and multiphoton microscopy can have clinical diagnostic applications. The successful combination of both modalities in tissue imaging enables unique image contrast to be achieved, especially if a single laser excitation wavelength is used. We apply this approach for skin and corneal imaging using the 780-nm output of a femto...

We performed multiphoton imaging on fungi of medical significance. Fungal hyphae and spores of Aspergillus flavus, Micosporum gypseum, Micosoprum canis, Trichophyton rubrum, and Trichophyton tonsurans were found to be strongly autofluorescent but generate less prominent second harmonic signal. The cell wall and septum of fungal hyphae can be easily...

Recently, multiphoton microscopy has gained much popularity as a noninvasive imaging modality in biomedical research. We evaluate the potential of multiphoton microscopy for monitoring laser-skin reaction in vivo. Nude mouse skin is irradiated with an erbium:YAG laser at various fluences and immediately imaged by a multiphoton microscope. The alter...

Plasmonic photothermal therapy is a new cancer thermotherapy method based on surface plasmon resonance of nanoparticles. It is important to measure the temperature during thermotherapy for safety and efficacy. In this study, we apply a photoacoustic (PA) method for real-time, non-invasive temperature measurements. In particular, this method can be...

We describe a case of granulomatous slack skin in a 31-year-old woman with an unusual presentation of acquired ichthyosis and muscular masses involving four limbs over 3 years. Vesicles and ulcerative skin nodules first appeared only 3 months prior to diagnosis. The diagnosis was confirmed after sequential biopsies of muscle, skin lesions, and lymp...

Tumor-associated macrophages (TAMs) and cyclooxygenase-2 (COX-2) are associated with invasion, angiogenesis, and poor prognosis in many human cancers. However, the role of TAMs in human basal cell carcinoma (BCC) remains elusive. We found that the number of TAMs infiltrating the tumor is correlated with the depth of invasion, microvessel density, a...

Stromal cell-derived factor 1alpha (SDF-1alpha) (CXCL12) has been observed to enhance tumor angiogenesis. However, the comprehensive role of SDF-1alpha (CXCL12)-CXCR4 interaction, exerted during angiogenesis, has not been well understood. We have previously demonstrated that human basal cell carcinoma (BCC) tissues and a BCC cell line (BCC-1/KMC) h...

The depilatory cream thioglycolate has been shown to be an effective enhancer for transdermal drug delivery. However the mechanism remains unknown. In addition, it may also increase the risk of permeation of exogenous toxic agents across skin in depilatory cream users. The aim of this study was to characterize its effect on the transepidermal route...

The aim of this study is to characterize the ability of multiphoton microscopy in monitoring the transdermal penetration enhancing effect of a depilatory agent and the associated structural alterations of stratum corneum. The result is compared with the electron microscopic findings. Our results show that the penetration of both hydrophilic and hyd...

Collagen is the most abundant protein in mammalian and forms various types of tissues. On ocular surface, sclera, limbus and cornea are composed with fibril form collagen. However, unlike other connective tissues with high opacity, cornea has extraordinary high transparency which originates from the regular arrangement of collagen fibers within cor...

In this study, we combined two-photon autofluorescence and second harmonic generation imaging to investigate the three-dimensional microstructure and nonlinear optical properties of tissue engineering scaffolds. We focused on five different types of scaffold materials commonly used in tissue engineering, including: open-cell polylactic acid, polygl...

In recent years, the non-linear optical imaging technique of multiphoton microscopy has gained significant popularity in biomedical imaging. Since optical imaging can provide detailed morphological information of biological structures, multiphoton microscopy holds great promise as a potential clinical diagnostic tool of dermatological conditions. I...

Transdermal drug delivery provides a non-invasive route of drug administration, and can be a alternative method to oral delivery and injection. The stratum corneum (SC) of skin acts as the main barrier to transdermal drug delivery. Studies suggest that depilatory enhances permeability of drug through the epidermis. However, transdermal delivery pat...

Early mycosis fungoides (MF) is difficult to distinguish from other benign inflammatory dermatoses. We evaluated clonal T-cell receptor (TCR) gamma gene rearrangement by polymerase chain reaction (PCR) as a surrogate to histologic diagnosis in early MF. Twenty paraffin-embedded skin biopsies from nine patients diagnosed with MF were included. Two m...

Using the technique of second-harmonic generation (SHG) microscopy we obtained large area image of type I collagen from rat tail tendon as it is heated from 40°C to 70°C for 0 to 180 minutes. The high resolution images allowed us to investigate the collagen structural change. We observed that heating the tendon below the temperature of 54°C does no...

Reflected confocal microscopy has been widely used in clinical application in dermatology. In recent years, multiphoton microscopy has also emerged as an important minimally invasive bioimaging technique for the skin. In this study, we combine reflected confocal microscopy and multiphoton microscopy for skin imaging. In the epidermis, reflected con...

For secure removal of the basal cell carcinoma tissue, the technique of Mohs' micrographic surgery is often used. However, Mohs' micrographic surgery is time-consuming. In this work, we evaluate the ability of multiphoton fluorescence (MF) and second harmonic generation (SHG) imaging to discriminate the borders of human basal cell carcinoma. Morpho...

The purpose of this study is to demonstrate the application of multiphoton fluorescence and second harmonic generation (SHG) microscopy for the ex-vivo visualization of human corneal morphological alterations due to infectious processes. The structural alterations of both cellular and collagenous components can be respectively demonstrated using fl...

The aim of this work is to image the wound healing process of cornea in an in vitro organ culture model with noninvasive multiphoton imaging modality. Autofluorescence and second harmonic generation (SHG) were respectively used to monitor the alterations of cellular and collagenous components during wound healing processes. Within additional develo...

The aim of this study is to assess the application of multiphoton autofluorescence and second harmonic generation (SHG) microscopy for investigating the structural alterations and the pattern of microbial spreading during corneal infectious process in an in vitro organ culture model. The autofluorescence spectrum derived from pathogens allows us to...

To demonstrate the application of multiphoton fluorescence (MF) and second harmonic generation (SHG) microscopy for ex vivo characterization of the structural alterations of human corneas due to keratoconus. Buttons of keratoconic corneas derived from penetrating keratoplasty were sent for structural analysis with a custom-built multiphoton microsc...

In this work, we compared the performance of objectives with similar numerical aperture of 0.75 but different immersion media of air, water, glycerin, and oil in the imaging of human skin epithelium and dermis. In general, we found that the oil immersion objective recorded the strongest intensity at the same mechanical depth. We also characterized...

We attempt to characterize the degree of skin thermal damage by using multiphoton microscopy to characterize dermal thermal damage. Our results show that dermal collagen and elastic fibers display different susceptibility to thermal injury. Morphologically, dermal collagen starts to denature at 60 degrees C while fracture and aggregation of elastic...

We apply the technique of second-harmonic generation (SHG) microscopy to obtain large area submicron resolution image of Type I collagen from rat tail tendon as it is heated from 40 degrees C to 70 degrees C for 0-180 min. The change in the collagen structure as reflected in its SHG image is observed at length scales from submicron to hundreds of m...

Though reported limitedly in tissue engineering, modification of cellular functions can be achieved by culturing them into multicellular spheroids. We have shown melanocytes form spheroids on chitosan surface. However, how biomaterials promote spheroid formation has never been systemically investigated. In this work, nylon, which inhibits melanocyt...

We performed multiphoton fluorescence (MF) and second-harmonic generation (SHG) imaging on human basal cell carcinoma samples. In the dermis, basal cell carcinomas can be identified by masses of autofluorescent cells with relatively large nuclei and marked peripheral palisading. In the normal dermis, SHG from dermal collagen contributes largely to...

We describe the case of a 13-year-old boy with stage I hypopigmented mycosis fungoides in whom minimal residual disease was detected with T-cell receptor gamma-polymerase chain reaction after the disease was in complete clinical remission. We further cloned and sequenced the T-cell receptor gamma-polymerase chain reaction product of the lesion in r...

Cyclooxygenase-2 (COX-2) is critical for tumor formation, angiogenesis, metastasis, and prognosis. In this study, the role of COX-2 in antiapoptosis, tumorigenesis, and angiogenesis of human basal cell carcinoma (BCC) cells was investigated. Transfection of COX-2 constitutive expression vector into a BCC cell line yielded several overexpressing clo...

Collagen shrinkage associated with denaturation from thermal treatment has a number of important clinical applications. However, individualized treatment is hindered by the lack of reliable noninvasive methods to monitor the process of collagen denaturation. We investigate the serial changes of collagen denaturation from thermal treatment of rat ta...

The anticonvulsant carbamazepine (CBZ) frequently causes cutaneous adverse drug reactions (cADRs), including maculopapular eruption (MPE), hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We reported that SJS/TEN caused by CBZ is strongly associated with the HLA-B*1502 gene in Han Chinese. Here,...

An outbreak of suspected contact dermatitis among subway construction workers was suspected to be due to a new bisphenol A/F-based epoxy resin system (ERS). The construction workers used ERSs during the insertion of iron bars into concrete walls. The objective of the study was to determine the components (if any) of the ERS responsible for the cont...

The purpose of this work was to demonstrate the use of the combined imaging modality of multiphoton autofluorescence and second-harmonic generation (SHG) microscopy in obtaining spectrally resolved morphologic features of the cornea, limbus, conjunctiva, and sclera in whole, ex vivo porcine eyes. The 780-nm output of a femtosecond, titanium-sapphir...

Autologous melanocyte transplantation for vitiligo treatment by use of melanocyte suspension has drawbacks including cell damage in cell preparation and transportation, difficult manipulation and low engraftment rate in acral vitiligious lesions. We have proposed the concept of cellular patch as an alternative solution. In the development of melano...

The purpose of this study is to assess the application of multiphoton fluorescence and second harmonic generation (SHG) microscopy for imaging and monitoring the disease progress of infectious keratitis in an experimental model, and to investigate the possible correlation of tissue architecture with spreading patterns of pathogens in an experimenta...

Multiphoton autofluorescence and second harmonic generation (SHG) microscopy are useful in respectively identifying elastin and collagen fibers within the skin dermis. In this study, we attempt to characterize the degree of skin thermal damage by using multiphoton microscopy to characterize the thermal changes to collagen and elastin fibers. We fou...

It is a field of great interest to develop therapies to rejuvenate photoaged skin. However, the treatment response can not be ideally determined due to lack of a reliable non-invasive method to quantify photoaging. In this study, the photoaging process of skin is investigated by use of a multiphoton fluorescence and second harmonic generation micro...

Thermal treatment induced collagen shrinkage has a great number of applications in medical practice. Clinically, the there is lack of reliable non-invasive methods to quantify the shrinkage. Overt treatment by heat application can lead to devastating results. We investigate the serial changes of collagen shrinkage by thermal treatment of rat tail t...

The purpose of this study is to assess the possible application of multiphoton fluorescence and second harmonic generation (SHG) microscopy for imaging the structural features of keratoconus cornea and to evaluate its potential as being a clinical in vivo monitoring technique. Using the near-infrared excitation source from a titanium-sapphire laser...

The advantages offered by multiphoton microscopy enabled this technique to be applied for in vivo understanding of physiological processes. However, multiphoton intravital microscopy also requires associated technologies to be developed. In this work, we detailed the design of a dorsal skin fold chamber made of titanium alloy that allow high resolu...

We characterize the structural changes of porcine corneal structures from 25 to 90 degrees C using second harmonic generation (SHG) microscopy. Our results show that porcine stroma undergoes several distinct stages of structural changes between 25 and 90 degrees C. A decrease in SHG intensity from 30 to 45 degrees C and the existence of SHG intensi...

The photoaging process of facial skin is investigated by use of multiphoton fluorescence and second-harmonic generation (SHG) microscopy. We obtain the autofluorescence (AF) and SHG images of the superficial dermis from the facial skin of three patients aged 20, 40, and 70 years . The results show that areas of AF increase with age, whereas areas o...

Multiphoton microscopy has evolved into a powerful bioimaging tool in three dimensions. However, the ability to image biological specimens in-depth can be hindered by sample spherical aberration and scattering. These two phenomena can result in the degradation of image resolution and the loss of detected multiphoton signal. In this work, we use the...

The search for biocompatible materials that can maintain function of melanocytes as the cellular patch is a feasible alternative for use in the autologous melanocyte transplantation for vitiligo. In this study, we demonstrated that the surface of chitosan-coated polystyrene wells supported the growth and phenotype expression of melanocytes. Dependi...

Physical and chemical enhancement techniques have proven to be useful in promoting transdermal delivery of therapeutic agents. However, it has been difficult to follow the changes to the skin during these processes microscopically. In this work, we use multiphoton polarization (P) and generalized polarization (GP) imaging of the membrane probe Laur...

As a major component of the connective tissues, collagen fibers are responsible for various physiological functions inside the body. They provide support for the skin, partial focusing through the cornea, and coordinate movements via tendons, ligaments, and cartilages. In many medical procedures, thermal reorganization of the collagen structure is...

This purpose of this study is to demonstrate the feasibility of using multiphoton microscopy in ophthalmologic imaging. Without the introduction of extrinsic fluorescence molecules, multiphoton induced autofluorescence and second harmonic generation signals can be used to obtain useful structural information of normal and diseased corneas. Our work...

In recent years, non-linear imaging techniques such as multiphoton fluorescence and harmonic generation microscopy have been successfully applied to dermatological imaging. Confocal-like image quality, enhanced depth penetration, and non-linear spectral signatures are among the main advantages of this family of techniques. In this presentation, we...

The thermal disruption of collagen I in rat tail tendon is investigated with second-harmonic generation (SHG) microscopy. We investigate its effects on SHG images and intensity in the temperature range 25 ° – 60 ° C . We find that the SHG signal decreases rapidly starting at 45 ° C . However, SHG imaging reveals that breakage of collagen fibers is...

Two-photon autofluorescence and second harmonic generation (SHG) microscopy are useful imaging techniques for studying tissue components. In this work, we apply this imaging modality to study porcine eye. In particular, we use SHG microscopy to investigate the structural changes to excised porcine corneas and found that this technique is useful for...

Luminescent quantum dots (QDs) are attractive fluorescent probes in bioimaging application. In this work, we investigate the feasibility of administering QDs (7 nm in size) through transdermal delivery pathway using multiphoton fluorescence imaging. Our results show that QDs of this size range can be effectively delivered through intercellular path...

Multiphoton microscopy is to a powerful imaging modality in the life sciences. The improved image contrast, greater imaging depths, and focus limited photodamage enable multiphoton microscopy to be especially useful for in vivo bioimaging applications. For multiphoton microscopy to be widely applicable in for in vivo biopsy applications, characteri...

In this work, the thermal disruption of type I collagen is investigated using second harmonic generation (SHG) microscopy. We investigated the effects of second harmonic generation images and intensity of rat tail tendon in the temperature range from 25 to 60°C. We found a structural transition at 57°C where a drop in second harmonic intensity is c...

Multiphoton microscopy is a three-dimensional imaging technique with a number of advantages. For example, multiphoton microscopy can image tissues up to a depth of a few hundred micrometers, at high resolution and with improved contrast. In this work, we used multiphoton microscopy in investigating the actions of the chemical enhancer oleic acid in...

This purpose of this study is to demonstrate the feasibility of using multiphoton microscopy in imaging eye surface. Specifically, the cornea, limbus, conjunctiva, and sclera were imaged using multiphoton induced fluorescence and second-harmonic generation (SHG) imaging.

For many years, the dorsal skinfold chamber has been used for intravital observation in animal models. We have developed a chamber built using medical-grade titanium. Our design allows long-term, high resolution, and large-area observation in nude mice in vivo. Combined with two-photon fluorescence and second-harmonic generation microscopy, our cha...

Drug delivery through skin has benefits such as its conveniences of providing controlled dosage to patients. In this article we investigate the effects of electrical characteristics of molecules on their effectiveness in transdermal drug delivery. Using multiphoton microscopy, we imaged the skin treated with fluorescent model drugs having different...

We have previously demonstrated a xenograft of interleukin-6 (IL-6) overexpressing basal cell carcinoma (BCC) cell line induced tumors with high vasculature in nude mice. Here we asked whether IL-6 could induce angiogenic activity in BCC cell line. Tenfold concentrated conditioned medium (CM) from IL-6 overexpressing BCC cells exhibited higher angi...

Multiphoton microscopy is a powerful technique for achieving three-dimensional submicron imaging in biological specimens. However, specimen optical parameters such as refractive indices and scattering coefficients can result in the loss of image resolution and decreased signal in depth. These factors are coupled to the focusing objective's numerica...

Atopic dermatitis (AD) is a complex disease with both a genetic background and environmental interactions. Although multiple linkage-analyses about AD have been studied, there have been only a few family aggregation tests of AD or perennial allergic rhinitis (AR) to date. The association of allergen-specific IgE in AD and atopic dermatitis with all...