Wounding enhances epidermal tumorigenesis by recruiting hair follicle keratinocytes

Chronic wounds and acute trauma constitute well-established risk factors for development of epithelial-derived skin tumors, although the underlying mechanisms are largely unknown. Basal cell carcinomas (BCCs) are the most common skin cancers displaying a number of features reminiscent of hair follicle (HF)-derived cells and are dependent on deregulated Hedgehog (Hh)/GLI signaling. Here we show, in a mouse model conditionally expressing GLI1 and in a model with homozygous inactivation of Ptch1, mimicking the situation in human BCCs, that the wound environment accelerates the initiation frequency and growth of BCC-like lesions. Lineage tracing reveals that both oncogene activation and wounding induce emigration of keratinocytes residing in the lower bulge and the nonpermanent part of the HFs toward the interfollicular epidermis (IFE). However, only oncogene activation in combination with a wound environment enables the participation of such cells in the initiation of BCC-like lesions at the HF openings and in the IFE. We conclude that, in addition to the direct enhancement of BCC growth, the tumor-promoting effect of the wound environment is due to recruitment of tumor-initiating cells originating from the neighboring HFs, establishing a link between epidermal wounds and skin cancer risk.     

Basal cell carcinoma - molecular biology and potential new therapies

Basal cell carcinoma (BCC) of the skin, the most common malignancy in individuals of mixed European descent, is increasing in incidence due to an aging population and sun exposure habits. The realization that aberrant activation of Hedgehog signaling is a pathognomonic feature of BCC development has opened the way for exciting progress toward understanding BCC biology and translation of this knowledge to the clinic. Genetic mouse models closely mimicking human BCCs have provided answers about the tumor cell of origin, and inhibition of Hedgehog signaling is emerging as a potentially useful targeted therapy for patients with advanced or multiple BCCs that have hitherto lacked effective treatment.     

Nanoporous Carbide-Derived Carbon Material-Based Linear Actuators

Devices using electroactive polymer-supported carbon material can be exploited as alternatives to conventional electromechanical actuators in applications where electromechanical actuators have some serious deficiencies. One of the numerous examples is precise microactuators. In this paper, we show for first time the dilatometric effect in nanocomposite material actuators containing carbide-derived carbon (CDC) and polytetrafluoroetylene polymer (PTFE). Transducers based on high surface area carbide-derived carbon electrode materials are suitable for short range displacement applications, because of the proportional actuation response to the charge inserted, and high Coulombic efficiency due to the EDL capacitance. The material is capable of developing stresses in the range of tens of N cm^-2. The area of an actuator can be dozens of cm², which means that forces above 100 N are achievable. The actuation mechanism is based on the interactions between the high-surface carbon and the ions of the electrolyte. Electrochemical evaluations of the four different actuators with linear (longitudinal) action response are described. The actuator electrodes were made from two types of nanoporous TiC-derived carbons with surface area (S_A) of 1150 m² g^-1 and 1470 m² g^-1, respectively. Two kinds of electrolytes were used in actuators: 1.0 M tetraethylammonium tetrafluoroborate (TEABF₄) solution in propylene carbonate and pure ionic liquid 1-ethyl-3-methylimidazolium trifluoromethanesulfonate (EMITf). It was found that CDC based actuators exhibit a linear movement of about 1% in the voltage range of 0.8 V to 3.0 V at DC. The actuators with EMITf electrolyte had about 70% larger movement compared to the specimen with TEABF₄ electrolyte.     

Uric acid is associated with microalbuminuria and decreased glomerular filtration rate in the general population during 7 and 13 years of follow-up: The Tromsø Study

Background

The role of uric acid in development of renal dysfunction (RD) remains controversial. Earlier studies have reported inconsistent results, possibly because of their varying ability to adjust for confounding. The impact of longitudinal change in uric acid on renal outcome has not been assessed previously. We aimed to study the impact of change in serum uric acid (SUA) as well as baseline SUA on the development of RD.

Methods

In a prospective cohort study, we assessed the associations between change in SUA during follow-up, baseline SUA and RD (defined as albumin-creatinine-ratio (ACR) ≥1.13 mg albumin/mmol creatinine and/or eGFR?<?60 ml/min/1.73 m²) in a large cohort from a general population participating in the Tromsø Study (n?=?2637). Participants were stratified according to tertiles of change in SUA between baseline (1994/95) and follow-up 13 years later. (upper tertile: SUA increasing group, two lower tertiles: SUA non-increasing group). Logistic regression analysis was applied with RD and each component of RD after 7 and 13 years as the dependent variables. Adjustments were made for baseline eGFR, cardiovascular risk factors, and the use of antihypertensive drugs including diuretics.

Results

After excluding participants with RD at baseline, SUA increasers, compared to SUA non-increasers, had a doubled risk of RD after 7 years (odds ratio 2.00, (95 % CI 1.45, 2.75)). Odds ratio for RD in SUA increasers after 13 years was 2.18 (95 % CI 1.71, 2.79). The risk of developing ACR ≥1.13 mg/mmol alone was not significantly increased after 7 years (odds ratio 1.30 (95 % CI 0.90, 1.89), but after 13 years (odds ratio 1.43 (95 % CI 1.09, 1.86)). An increase in baseline SUA of 59 μmol/L (1 mg/dL) gave an odds ratio for RD after 13 years of 1.16 (95 % CI 1.04, 1.29).

Conclusion

An increase in SUA during follow-up was associated with an increased risk of developing RD after 7 and 13 years.