Vascular regeneration and skeletal muscle repair induced by long-term exposure to SDF-1α derived from engineered mesenchymal stem cells after hindlimb ischemia.

Despite recent progress in medical and endovascular therapy, the prognosis for patients with critical limb ischemia (CLI) remains poor. In response, various stem cells and growth factors have been assessed for use in therapeutic neovascularization and limb salvage in CLI patients. However, the clinical outcomes of cell-based therapeutic angiogenesis have not provided the promised benefits, reinforcing the need for novel cell-based therapeutic angiogenic strategies to cure untreatable CLI. In the present study, we investigated genetically engineered mesenchymal stem cells (MSCs) derived from human bone marrow that continuously secrete stromal-derived factor-1α (SDF1α-eMSCs) and demonstrated that intramuscular injection of SDF1α-eMSCs can provide long-term paracrine effects in limb ischemia and effectively contribute to vascular regeneration as well as skeletal muscle repair through increased phosphorylation of ERK and Akt within the SDF1α/CXCR4 axis. These results provide compelling evidence that genetically engineered MSCs with SDF-1α can be an effective strategy for successful limb salvage in limb ischemia.

Raphani Semen (Raphanus sativus L.) Ameliorates Alcoholic Fatty Liver Disease by Regulating De Novo Lipogenesis.

In this study, we investigated the pharmacological effect of a water extract of Raphani Semen (RSWE) on alcoholic fatty liver disease (AFLD) using ethanol-induced AFLD mice (the NIAAA model) and palmitic acid (PA)-induced steatosis HepG2 cells. An RSWE supplement improved serum and hepatic triglyceride (TG) levels of AFLD mice, as well as their liver histological structure. To explore the molecular action of RSWE in the improvement of AFLD, we investigated the effect of RSWE on four major pathways for lipid homeostasis in the liver: free fatty acid transport, lipogenesis, lipolysis, and ß-oxidation. Importantly, RSWE decreased the mRNA expression of de novo lipogenesis-related genes, such as Srebf1, Cebpa, Pparg, and Lpin1, as well as the protein levels of these factors, in the liver of AFLD mice. That these actions of RSWE affect lipogenesis was confirmed using PA-induced steatosis HepG2 cells. Overall, our findings suggest that RSWE has the potential for improvement of AFLD by inhibiting de novo lipogenesis.

Comparison of Surgical Outcomes and Survival between Octogenarians and Younger Patients after Pulmonary Resection for Stage I Lung Cancer.

BACKGROUND: Treatment strategies for octogenarians with lung cancer remain controversial. The purpose of this study was to compare surgical outcomes and survival between octogenarians and younger patients with stage IA and IB lung cancer. METHODS: We reviewed the medical records of 34 consecutive octogenarians and 457 younger patients (<70 years) with stage I lung cancer who underwent surgical resection from January 2007 to December 2015. We analyzed the survival and surgical outcomes of the 2 groups according to the lung cancer stage (IA and IB). RESULTS: The only significant differences in the clinicopathological features between the groups were the higher proportion of sublobar resection (56.3% vs. 18.9%) and the smaller number of dissected lymph nodes (LNs) in octogenarians. There was no significant difference in hospital stay (11 days vs. 9 days), pneumonia (5.8% vs 1.9%), or operative mortality (0% vs 0.6%) between the 2 groups. Among patients with stage IA lung cancer, 5-year recurrence-free survival was not significantly different between the octogenarians (n=16) and younger patients (n=318) (86.2% vs. 89.1%, p=0.548). However, 5-year overall survival was significantly lower in octogenarians than in younger patients (79.4% vs. 93.4%, p=0.009). Among patients with stage IB lung cancer, there was no significant difference in 5-year recurrence-free survival (62.1% vs. 73.5%, p=0.55) or overall survival (77.0% vs 85.0%, p=0.75) between octogenarians (n=18) and younger patients (n=139). In multivariable analysis, male sex, the number of dissected LNs, and tumor size were factors related to survival (hazard ratio [HR], 5.795; p=0.017; HR, 0.346, p=0.025; and HR, 1.699; p=0.035, respectively). CONCLUSION: Surgical outcomes and survival after pulmonary resection for stage I lung cancer were comparable in octogenarians and younger patients. Continued careful selection of octogenarians for pulmonary resection is important to achieve good results.

Synergistic Effect of Bupleuri Radix and Scutellariae Radix on Adipogenesis and AMP-Activated Protein Kinase: A Network Pharmacological Approach.

Obesity has become a major health threat in developed countries. However, current medications for obesity are limited because of their adverse effects. Interest in natural products for the treatment of obesity is thus rapidly growing. Korean medicine is characterized by the wide use of herbal formulas. However, the combination rule of herbal formulas in Korean medicine lacks experimental evidence. According to Shennong's Classic of Materia Medica, the earliest book of herbal medicine, Bupleuri Radix (BR) and Scutellariae Radix (SR) possess the Sangsoo relationship, which means they have synergistic features when used together. Therefore these two are frequently used together in prescriptions such as Sosiho-Tang. In this study, we used the network pharmacological method to predict the interaction between these two herbs and then investigated the effects of BR, SR, and their combination on obesity in 3T3-L1 adipocytes. BR, SR, and BR-SR mixture significantly decreased lipid accumulation and the expressions of two major adipogenic factors, peroxisome proliferator-activated receptor-gamma (PPARγ) and CCAAT/enhancer-binding protein-alpha (C/EBPα), and their downstream genes, Adipoq, aP2, and Lipin1 in 3T3-L1 cells. In addition, the BR-SR mixture had synergistic effects compared with BR or SR on inhibition of adipogenic-gene expressions. BR and SR also inhibited the protein expressions of PPARγ and C/EBPα. Furthermore, the two extracts successfully activated AMP-activated protein kinase alpha (AMPK α), the key regulator of energy metabolism. When compared to those of BR or SR, the BR-SR mixture showed higher inhibition rates of PPARγ and C/EBPα, along with higher activation rate of AMPK. These results indicate a new potential antiobese pharmacotherapy and also provide scientific evidence supporting the usage of herbal combinations instead of mixtures in Korean medicine.

Analysis of the monocyte chemoattractant protein 1 -2518 promoter polymorphism in Korean patients with alopecia areata.

Monocyte chemoattractant protein-1 (MCP-1) levels are increased in scalp lesions of patients with alopecia areata (AA), suggesting a role in the development of AA. Recently, a biallelic A/G polymorphism in the MCP-1 promoter at position -2518 has been found, influencing the level of MCP-1 expression in response to an inflammatory stimulus. We investigated whether the presence of these polymorphisms were associated with AA in Korean population. 145 Korean patients with AA, 246 healthy subjects without clinical evidence of AA were screened for genotype with a PCR-based assay. In the AA patients the frequency of the A and G alleles was 40.3 and 59.7%, respectively and the distribution of the A/A, A/G and G/G genotypes was 19.3, 42.1 and 38.6%, respectively. Amongst the controls the frequency of the A and G alleles was 39.8 and 60.2%, and the distribution of the A/A, A/G, G/G genotypes in the same group was 17.5, 44.7 and 37.8%, respectively. There was no significant difference in the allele frequencies and genotype distributions between the patients and the controls (p=0.889, p=0.848, respectively). Our data indicates that no association exists between the -2518A/G polymorphism of the MCP-1 gene and susceptibility to alopecia areata.

Topical aminolevulinic acid-photodynamic therapy for the treatment of acne vulgaris.

BACKGROUND: Photodynamic therapy (PDT) is useful for the treatment of epidermal neoplasia but may also have use in the treatment of inflammatory dermatoses. The purpose of this study was to evaluate the safety and efficacy of PDT in the treatment of acne on the face. METHODS: Eight patients with mild-to-moderate acne vulgaris on the face were treated with one session of topical aminolevulinic acid (ALA)-PDT using a red light. Each patient's face was divided into two areas (right side and left side) for ALA-PDT and untreated control. Twenty percent topical ALA was applied with 4 h occlusion, and 18 J/cm(2) red light (630+/-63 nm) was administered. Each patient's acne was visually assessed by a spot count of both inflamed and non-inflamed lesions at baseline and at 1, 3, and 6 months following PDT. RESULTS: At 1, 3, and 6 months, the mean percentage reduction in inflamed lesions count was 27.6%, 37.9%, and 41.9%, respectively, in the ALA-PDT-treated area, whereas in the control area, it was 8.0%, 14.7%, and 15.4%, respectively, compared with the baseline. This showed a higher reduction of a spot count of inflamed lesions in the ALA-PDT-treated area, which was statistically significant (P<0.05). There was a slightly higher reduction of a spot count of non-inflamed lesions in the ALA-PDT-treated area, which was statistically not significant (P>0.05). The adverse effects were minimal. CONCLUSION: ALA-PDT with red light was found to be effective in the reduction of the number of inflamed lesions in patients with mild-to-moderate acne vulgaris, with no significant short-term adverse effects.

Short-term effects of 308-nm xenon-chloride excimer laser and narrow-band ultraviolet B in the treatment of vitiligo: a comparative study.

We compared the clinical efficacy of a short-term intervention of 308-nm excimer laser with that of narrow-band UVB (NBUVB) phototherapy for vitiligo patients to see the early response. Twenty-three symmetrically patterned patches of vitiligo on 8 patients were selected. Vitiligo patches on one side of the body were treated 2 times per week for a maximum of 20 treatments with the excimer laser, and NBUVB phototherapy was used on patches on the other side. Improvement (repigmentation) was assessed on a visual scale via serial photographs taken every five treatments and scored as follows: 0,< or =1% improvement; 1,< or =25% improvement; 2, 26-50% improvement; 3, 51-75% improvement; and 4, > or =75% improvement. At five treatments, the excimer laser-treated patches had an average score of 0.26, compared with 0.04 for patches treated with NBUVB phototherapy. A slightly higher repigmentation (p>0.05) in the excimer treated area was thus observed. At 10, 15, or 20 treatments, the differences between the average scores were significant: 0.83, 1.17, and 1.39 for the excimer-treated patches, and 0.17, 0.30, and 0.74 for the NBUVB phototherapy-treated areas (p<0.05). In conclusion, the 308-nm excimer laser appears to be more effective than NBUVB phototherapy, as it produces more rapid and profound repigmentation.

Differential expression of TGF-beta isoforms during differentiation of HaCaT human keratinocyte cells: implication for the separate role in epidermal differentiation.

The three mammalian isoforms of transforming growth factor-beta(TGF-beta1, beta2, beta3) are potent regulators of cell growth, differentiation, and extracellular matrix deposition. To study their role in skin differentiation, we investigated the expression of TGF-beta isoforms on cell growth and differentiation induction of the human keratinocyte cell line, HaCaT by elevating the Ca(2+) concentration. An ELISA and RT-PCR assay revealed secreted TGF-beta 1 protein and TGF-beta 1 mRNA were increased during calcium-induced differentiation. In contrast, major differences were seen for TGF-beta 2 and TGF-beta 3 mRNA which were decreased during differentiation, but TGF-beta 2 and TGF-beta3 protein were not evident on an ELISA. These results suggest different functions for each TGF-beta isoforms in epidermal differentiation, such that TGF-beta 1 is associated with the more differentiated state, and TGF-beta 2 and TGF-beta 3 may be associated the more proliferated state.

A case of propylthiouracil-induced pyoderma gangrenosum associated with antineutrophil cytoplasmic antibody.

A 27-year-old woman who had been receiving propylthiouracil for 2 years for Graves' disease presented with painful ulceration on the lower limbs which had first appeared 2 weeks previously. Well-circumscribed hemorrhagic ulcerations with ragged borders were noted on both legs. Skin biopsy demonstrated a florid neutrophilic infiltrate and evidence of leukocytoclasis around small blood vessels in the papillary dermis compatible with the diagnosis of pyoderma gangrenosum. A highly positive perinuclear pattern of antineutrophil cytoplasmic antibody with specificities for IgM myeloperoxidase was observed. The authors think that propylthiouracil is associated with the occurrence of pyoderma gangrenosum in this patient.

Acquired perforating dermatosis in patients with chronic renal failure and diabetes mellitus.

Acquired perforating dermatosis (APD) is a skin disorder occurring in the patients with chronic renal failure (CRF), diabetes mellitus (DM) or both. The purpose of this study was to clarify the clinical and histopathological features of APD, and evaluate role of scratching in the pathogenesis of APD. Twelve patients with APD associated with CRF and DM were enrolled in the study. In six patients who required hemodialysis, the lesions appeared 2-5 yr (mean 3 yr) after the initiation of dialysis, 18-22 yr (mean 19.3 yr) after the occurrence of DM. The other patients who did not receive hemodialysis noted the lesions 4-17 yr (mean 9.5 yr) after the onset of DM. All patients had an eruption of generally pruritic keratotic papules and nodules, primarily on the extensor surface of the extremities and the trunk. The histologic features of our cases showed a crateriform invagination of the epidermis filled by a parakeratotic plug and basophilic cellular debris. The period of treatment for patients who suffered from severe (7 cases) or very severe (3 cases) on the pruritus intensity was longer than that of patients who had mild pruritus (2 cases). These data showed that scratching appear to play a critical part in the pathogenesis of APD.