Newborn microglia rapidly replenish the whole brain after selective elimination of most microglia (>99%) in adult mice. Previous studies reported that repopulated microglia were largely derived from microglial progenitor cells expressing nestin in the brain. However, the origin of these repopulated microglia has been hotly debated. In this study, we investigated the origin of repopulated microglia by a series of fate-mapping approaches. We first excluded the blood origin of repopulated microglia via parabiosis. With different transgenic mouse lines, we then demonstrated that all repopulated microglia were derived from the proliferation of the few surviving microglia (<1%). Despite a transient pattern of nestin expression in newly forming microglia, none of repopulated microglia were derived from nestin-positive non-microglial cells. In summary, we conclude that repopulated microglia are solely derived from residual microglia rather than de novo progenitors, suggesting the absence of microglial progenitor cells in the adult brain.

TWEAK (tumor necrosis factor-related weak inducer of apoptosis), a member of the tumor necrosis factor superfamily, acts on cells by binding to its only receptor named Fn14 (fibroblast growth factor-inducible 14). Their engagement activates a number of intracellular signal transduction cascades and consequently leads to cell death, proliferation, migration, or survival depending on the cellular contexts. Studies have indicated that the expression of TWEAK and Fn14 is upregulated in many solid tumors compared with healthy tissues. The activation of TWEAK/Fn14 signaling enhances the proliferation, invasion, and migration of tumor cells. Moreover, the angiogenesis, pro-inflammatory cytokine expression, and epithelial-mesenchymal transitions are promoted upon TWEAK/Fn14 activation. Currently, the tumor necrosis factor receptor-associated factor and nuclear factor kappa B signaling pathways are considered two main downstream pathways activated by TWEAK/Fn14 interaction. In view of these facts, some TWEAK- or Fn14-targeting agents are generated to inhibit the progression of tumors and have achieved initial success in clinical and pre-clinical trials. These agents include monoclonal antibodies, fusion proteins, immunotoxins, and nanoparticles. In addition, some relevant signaling pathways are studied to identify new potential therapeutic targets. Overall, these findings suggest that the TWEAK/Fn14 pathway is critical in the development of tumors, and targeting this signaling is a potential therapeutic approach in future tumor therapy.

The combination of NAFL with low-dose isotretinoin is a safe and effective treatment for moderate-to-severe acne.

Cell division cycle 20 (CDC20) is a regulatory molecule and serves critical roles at multiple points of the cell cycle. Recent evidence indicates that CDC20 may serve an oncogenic role in a number of human cancer types. However, the role of CDC20 in primary cutaneous squamous cell carcinoma (cSCC) has not been studied, to the best of our knowledge. The aim of the present study was to investigate whether and how CDC20 is involved in the tumorigenesis of cSCC. The results revealed that CDC20 expression was significantly increased in cSCC tissues and cell lines, and its expression was associated with pathological differentiation. Downregulation of CDC20 inhibited cell proliferation, induced cell cycle arrest, promoted apoptosis and reduced migratory ability through inhibition of the Wnt/β-catenin signaling pathway. Furthermore, all-trans-retinoic acid treatment significantly downregulated CDC20 expression in cSCC. The present results revealed that CDC20 may serve a crucial role in human cSCC, and suggested that CDC20 may be a novel biomarker for the prevention, diagnosis and treatment of cSCC.

Recent studies showed that TWEAK/Fn14 signaling participates in the progression of internal malignancies. However, its role in the biological properties of cutaneous squamous cell carcinoma (SCC) remains unclear. This study was designed to explore the effect of TWEAK/Fn14 activation on cutaneous SCC as well as the relevant mechanism. The expression of TWEAK and Fn14 was determined in tissue samples of patients with cutaneous SCC. Human primary keratinocytes and SCC cell lines were cultured in vitro, receiving stimulation of TWEAK. The xenografts of SCC were generated subcutaneously in BALB/c nude mice. The results showed that both TWEAK and Fn14 were highly expressed in human cutaneous SCC. Moreover, TWEAK/Fn14 activation promoted the proliferation, migration, and invasion of cultured SCC cells. Interestingly, TNFR2 was upregulated in cultured SCC cells, and the transfection of TNFR2 small interfering RNA abrogated the effect of TWEAK on these cells. Finally, the favorable effect of TWEAK/Fn14 signals was confirmed in BALB/c nude mice with SCC xenografts. In conclusion, TWEAK/Fn14 signals contribute to the progression of cutaneous SCC, possibly involving the TNF-aeindependent TNFR2 signal transduction.

We evaluated the short-term and long-term effects of the 1550 nm erbium:glass (Er:glass) fractional laser in the treatment of facial acne vulgaris. Forty-five (9 male and 36 female) acne patients were treated 4 times at 4-week intervals with the following parameters: 169 spot density and 15-30 mJ/cm(2) fluence. There was no control group. The laser spots were adjustable (maximum overlap: 20%) according to the treatment area, and delivered in rows in order to cover all the face. Clinical photographs were taken. The IGA scores and lesion counts were performed for each treatment. Their current state was obtained by phone call follow-up to determine the long-term effect and photographs were offered by themselves or taken in hospital. After four treatments, all patients had an obvious reduction of lesion counts and IGA score and the peak lesion counts decreased to 67.7% after the initial four treatment sessions. For long-term effect, 8 patients lost follow-up, hence 37 patients were followed-up. 8 patients were 2-year follow up, 27 at the 1-year follow-up, and all patients at the half-year follow-up. The mean percent reduction was 72% at the half-year follow-up, 79 at the 1-year follow-up and 75% at the 2-year follow-up. Side effects and complications were limited to transient erythema and edema, and few patients suffered from transient acne flare-ups and sensitivity. All patients responded that their skin was less prone to oiliness. In conclusion, acne can be successfully treated by 1550 nm Er:glass fractional laser, with few side effects and prolonged acne clearing.

The interaction between tumor necrosis factor- (TNF-) like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible 14 (Fn14) regulates the fate of keratinocytes, depending on the relative expression of TNF receptor (TNFR) 1 or TNFR2. However, the precise mechanism underlying this TWEAK-mediated regulation remains unclear. The aim of this study was to provide comprehensive insight into the roles of Fn14, TNFR1/2, and other relevant molecules in the fate of keratinocytes. Further, we sought to elucidate the structural basis for the interaction of TWEAK and Fn14 in regulating cellular outcomes. Normal keratinocytes (mainly expressing TNFR1) and TNFR2-overexpressing keratinocytes were stimulated with TWEAK. Through immunoprecipitation and Western blotting of keratinocyte lysates, we elucidated the associations between Fn14, TNFR-associated factor 2 (TRAF2), cellular inhibitor of apoptosis protein 1 (cIAP1), and TNFR1/2 molecules. Additionally, we found that TRAF2 exhibited binding to Fn14, cIAP1, and TNFR1/2. Our data suggest that TWEAK induces apoptosis in normal keratinocytes and proliferation in TNFR2-overexpressing keratinocytes in a TNF-α-independent manner; however, inhibition of TRAF2 appears to reverse this effect. Interestingly, the interaction between TWEAK and Fn14 increased TNFR1-associated death domain protein and caspase-8 expression in normal keratinocytes and promoted cytoplasmic import of cIAP1 in TNFR2-overexpressing keratinocytes. In conclusion, we found that the Fn14-TRAF2-TNFR signaling axis mediates TWEAK's regulation of the fate of keratinocytes, possibly in a manner involving the TNF-α-independent TNFR signal transduction.

No abstract