Overexpression of Smad2 Reveals Its Concerted Action with Smad4 in Regulating TGF- β-Mediated Epidermal Homeostasis

AbstractMembers of the transforming growth factor-β (TGF-β) superfamily are critical regulators for epithelial growth and can alter the differentiation of keratinocytes. Transduction of TGF-β signaling depends on the phosphorylation and activation of Smad proteins by heteromeric complexes of ligand-specific type I and II receptors. To understand the function of TGF-β and activin-specific Smad, we generated transgenic mice that overexpress Smad2 in epidermis under the control of keratin 14 promoter. Overexpression of Smad2 increases endogenous Smad4 and TGF-β1 expression while heterozygous loss of Smad2 reduces their expression levels, suggesting a concerted action of Smad2 and -4 in regulating TGF-β signaling during skin development. These transgenic mice have delayed hair growth, underdeveloped ears, and shorter tails. In their skin, there is severe thickening of the epidermis with disorganized epidermal architecture, indistinguishable basement membrane, and dermal fibrosis. These abnormal phenotypes are due to increased proliferation of the basal epidermal cells and abnormalities in the program of keratinocyte differentiation. The ectodermally derived enamel structure is also abnormal. Collectively, our study presents the first in vivo evidence that, by providing an auto-feedback in TGF-β signaling, Smad2 plays a pivotal role in regulating TGF-β-mediated epidermal homeostasis

Two Cases of Giant Epidermal Cyst Occurring in the Neck

Epidermal cysts are the most common cysts of the skin. Aconventional epidermal cyst rarely reaches a size of more than 5 cm in diameter. We report on two cases of giant epidermal cyst occurring in the neck. One patient had a cyst measuring 12×9×9 cm and the other patient had a non-pulsatile, dome-shaped lesion in the neck, which measured 6×5×3 cm. The lesions were totally excised. Histopathologically, both were confirmed as giant epidermal cysts

Clinicopathological Significance of Maspin Expression in Breast Cancer

Maspin is a unique serine proteinase inhibitor that has tumor suppressor activity. It has been reported that maspin is expressed in normal human mammary epithelial cells and it is down-regulated during the progression of cancer. However, to date, there is very limited data on the clinical significance of maspin expression in human breast cancer. In this study, maspin expression was assessed immunohistochemically from 80 invasive ductal carcinoma (IDC) specimens of the breast. Also, maspin expression was compared with the clinicopathological factors (age, grade, tumor size and lymph node status), the expression of estrogen receptor (ER), progesterone receptor (PR) and p53, DNA ploidy and the overall survival in an attempt to assess its prognostic value. The maspin expression was positive in 25 IDC cases (31.3%). The maspin expression in IDC was significantly correlated with a higher histologic grade, a larger tumor size, a positive p53 status and shorter survival. There was an inverse association with maspin expression and the PR status. These findings suggest that maspin expression is not down-regulated with the progression of cancer and maspin expression may be associated with a poor prognosis. The immunohistochemical detection of maspin in breast cancers may be helpful for predicting an aggressive phenotype

Screening of suitable cationic dopants for solar absorber material CZTS/Se: A first principles study

The earth abundant and non-toxic solar absorber material kesterite Cu2ZnSn(S/Se)(4) has been studied to achieve high power conversion efficiency beyond various limitations, such as secondary phases, antisite defects, band gap adjustment and microstructure. To alleviate these hurdles, we employed screening based approach to find suitable cationic dopant that can promote the current density and the theoretical maximum upper limit of the energy conversion efficiency (P(%)) of CZTS/Se solar devices. For this task, the hybrid functional (Heyd, Scuseria and Ernzerhof, HSE06) were used to study the electronic and optical properties of cation (Al, Sb, Ga, Ba) doped CZTS/Se. Our in-depth investigation reveals that the Sb atom is suitable dopant of CZTS/CZTSe and also it has comparable bulk modulus as of pure material. The optical absorption coefficient of Sb doped CZTS/Se is considerably larger than the pure materials because of easy formation of visible range exciton due to the presence of defect state below the Fermi level, which leads to an increase in the current density and P(%). Our results demonstrate that the lower formation energy, preferable energy gap and excellent optical absorption of the Sb doped CZTS/Se make it potential component for relatively high efficient solar cells

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

Loquat (Eriobotrya japonica) extracts suppress the adhesion, migration and invasion of human breast cancer cell line

We examined the inhibitory effects of loquat methanol extract on the adhesion, migration, invasion and matrix metalloproteinase (MMP) activities of MDA-MB-231 human breast cancer cell line. Cells were cultured with DMSO or with 10, 25, or 50 µg/ml of loquat methanol extract. Both leaf and seed extracts significantly inhibited growth of MDA-MB-231 cells in a dose-dependent manner, although leaf extract was more effective. Adhesion and migration were significantly inhibited by loquat extracts in a dose-dependent manner. Loquat extract also inhibited the invasion of breast cancer cells in a dose-dependent manner and leaf extract was more effective than seed extract. MMP-2 and MMP-9 activities were also inhibited by loquat extract. Our results indicate that methanol extracts of loquat inhibit the adhesion, migration and invasion of human breast cancer cells partially through the inhibition of MMP activity and leaf extract has more anti-metastatic effects in cell based assay than seed extract. Clinical application of loquat extract as a potent chemopreventive agent may be helpful in limiting breast cancer invasion and metastasis

A Case of Hepatocellular Carcinoma Within Hepatocellular Adenoma in a Non-Cirrhotic Male

Hepatocellular adenoma (HA) is a benign hepatic lesion that predominantly occurs in young women. Most hepatocellular carcinomas (HCC) arise in a cirrhotic liver during the fifth or sixth decades. There have been several reported cases of HCC developing from HA in female patients. However, there are rare cases about HCC arising in HA in a non-cirrhotic male patient. We have recently encountered a 53-year-old man who had a liver mass in a non-cirrhotic liver, and the liver mass was compatible with HA on the pre-operative computed tomography. The mass was completely resected and the histopathology revealed a focus of HCC arising in HA. We report here on this case along with a brief review of the relevant literature

Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters