Leptin promotes wound healing in the skin.

Leptin, a 16 kDa anti-obesity hormone, exhibits various physiological properties. Interestingly, skin wound healing was proven to delay in leptin-deficient ob/ob mice. However, little is known on the mechanisms of this phenomenon. In this study, we attempted to elucidate a role of leptin in wound healing of skin.Immunohistochemical analysis was performed to confirm the expression of the leptin receptor (Ob-R) in human and mouse skin. Leptin was topically administered to chemical wounds created in mouse back skin along with sustained-release absorbable hydrogel. The process of wound repair was histologically observed and the area of ulceration was measured over time. The effect of leptin on the proliferation, differentiation and migration of human epidermal keratinocytes was investigated.Ob-R was expressed in epidermal cells of human and mouse skin. Topical administration of leptin significantly promoted wound healing. Histological analysis showed more blood vessels in the dermal connective tissues in the leptin-treated group. The proliferation, differentiation/function and migration of human epidermal keratinocytes were enhanced by exogenous leptin.Topically administered leptin was proven to promote wound healing in the skin by accelerating proliferation, differentiation/function and migration of epidermal keratinocytes and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the skin

Sequence-dependent hydration water dynamics of dodecameric DNA

Hydration water dynamics were measured by quasi-elastic neutron scattering with H2O/D2O contrast for two DNA dodecamers, 5’CGCGAATTCGCG’3 and 5’CGCGTTAACGCG’3, which have been computationally shown to be structurally rigid and flexible, respectively. The dynamical transitions of the hydration water as well as DNA were observed for both sequences at approximately 240 K. Above the transition temperature, the mean square displacements of the hydration water for the rigid sequence were smaller than those for the flexible one. Furthermore, the relaxation time of the hydration water was longer in the rigid DNA than in the flexible DNA. We suggest that hydration water dynamics on the picosecond timescale are associated with sequence-dependent deformability of DNA

Effect of leptin on wound healing in mouse skin.

<p>(A) Chemical wounds created in mouse back skin by applying two pieces of filter paper (12x12mm each) soaked with 20% sodium hypochlorite for 5 minutes. (B and C) Skin wound healing at day 4 after wound creation. No significant difference in wound healing was noted between leptin-treated group and control group. Values are mean ± SE from 12 animals per group. (D and E) Skin wound healing at day 8 after wound creation. Significantly enhanced re-epithelialization of the wound was observed in leptin-treated group compared with control group. Values are mean ± SE from 12 animals per group. **P < 0.01. (F) Histological findings during wound repair at day 8 after wound creation. Spaces between the two arrowheads show ulcerated area without epithelial lining. H-E staining. (a) Leptin-reated group. (b) Control group. Scale bars = 500 μm.</p

Number of blood vessels in the dermal connective tissue beneath the ulcerated area.

<p>(A) At 4 days after initial wounding, no significant difference in the number of CD31-positive cells between Leptin-treated group and control group. (B) At 8 days, more CD31-positive cells were observed in the dermal connective tissue beneath the ulcerated area of leptin-treated group compared with control group. Values are mean ± SE from 5 animals per group. *P < 0.05. (C) Changes in body weight. (D) Changes in serum levels of blood sugar. (E) Changes in serum levels of AST. (F) Changes in serum levels of ALT. None of these laboratory parameters were significantly affected by leptin application. Values are mean ± SE from 5 animals per group.</p

Effect of leptin on the migration of human epidermal keratinocytes.

<p>Leptin enhanced the migration of cells. Values are mean ± SE from two independent experiments performed in triplicate. *P < 0.05</p

Oligonucleotide primers used in RT-PCR.

<p><i>F</i>: forward, <i>R</i>: reverse.</p><p>Oligonucleotide primers used in RT-PCR.</p

Lenalidomide and Dexamethasone for a Patient of POEMS Syndrome Presenting with Massive Ascites

POEMS syndrome is a multisystem disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. POEMS syndrome is a rare cause of refractory ascites. We report the case of a patient with POEMS syndrome presenting with massive ascites who was treated with very-low-dose lenalidomide and dexamethasone. A 57-year-old Japanese man was admitted to our hospital with pleural effusion, massive ascites, and leg edema. The diagnosis of POEMS syndrome was made based on the combination of the following findings: peripheral neuropathy, organomegaly, endocrinopathy, serum monoclonal protein elevation, skin changes, plasma VEGF elevation, and evidence of extravascular volume overload. Renal dysfunction induced by biopsy-proven renal involvement of POEMS syndrome was observed. Massive ascites of the patient dramatically diminished with long-time treatment of very-low-dose lenalidomide and dexamethasone. Lenalidomide seems to be a very promising therapy for POEMS syndrome presenting with extravascular volume overload such as edema, pleural effusion, and ascites. Very-low-dose lenalidomide might be effective especially for the patients with POEMS-related nephropathy

Oligonucleotide primers used in real-time RT-PCR.

<p><i>F</i>: forward, <i>R</i>: reverse.</p><p>Oligonucleotide primers used in real-time RT-PCR.</p

Effect of leptin on the expression of mRNA encoding <i>G3PDH</i> and <i>Cytokeratin 13</i>, <i>Cytokeratin 14</i> and <i>Transglutaminase I</i> in human epidermal keratinocytes.

<p>(A) Gene expression was analyzed by semi-quantitative RT-PCR analysis. (B-D) Effect of leptin on the expression of mRNA encoding <i>Cytokeratin 13</i> (B), <i>Cytokeratin 14</i> (C) and <i>Transglutaminase I</i> (D). Gene expression was analyzed by quantitative RT-PCR analysis. Values are mean expression ± SD of each gene (n = 8). ***P < 0.001.</p