PANX3 Channels Regulate Architecture, Adhesion, Barrier Function, and Inflammation in the Skin.

The channel-forming glycoprotein PANX3 functions in cutaneous wound healing and keratinocyte differentiation, but its role in maintaining skin homeostasis through aging is not yet understood. We found that PANX3 is absent in newborn skin but becomes upregulated with age. We characterized the skin of global Panx3-knockout (KO) mice and found that KO dorsal skin showed sex differences at different ages but generally had reduced dermal and hypodermal areas compared with age-matched controls. Transcriptomic analysis of the KO epidermis revealed reduced E-cadherin stabilization and Wnt signaling compared with that of wild-type, consistent with the inability of primary KO keratinocytes to adhere in culture and diminished epidermal barrier function in KO mice. We also observed increased inflammatory signaling in the KO epidermis and a higher incidence of dermatitis in aged KO mice compared with that in wild-type controls. These findings suggest that during skin aging, PANX3 is critical in the maintenance of dorsal skin architecture, keratinocyte cell-cell and cell-matrix adhesion, and inflammatory skin responses.

Hydrodynamic comparison of shunt and endoscopic third ventriculostomy in adult hydrocephalus using in vitro models and fluid-structure interaction simulation.

OBJECTIVE: The comparison of the efficiency of shunt placement and endoscopic third ventriculostomy (ETV) in treating of adult hydrocephalus patients with various intensities and different obstruction intensities in the aqueduct of Sylvius (AS). METHODS: In vitro models with separated ventricles were simulated and implemented for modeling shunt and ETV surgeries in one healthy subject and hydrocephalus patients with various intensities, as well as three different obstruction intensities in AS and under two cerebrospinal fluid (CSF) dynamic conditions. The fluid-structure interaction simulation was also carried out to validate in vitro results. RESULTS: The efficiency of both methods in reducing the maximum CSF pressure in the subarachnoid space (MCPS) decreased by an increase in the patient's intensities. Contrary to shunting, the efficiency of ETV in reducing MCPS demonstrated a decline (8.3-16.4%) by an increase in obstruction levels in AS. Based on the findings, shunt efficiency in decreasing MCPS in patients with low intensity was more remarkable compared to ETV. However, ETV was more efficient than shunt in the patient with intracranial hypertension. Further, shunt placement and ETV led to a significant reduction in the amplitude of CSF pressure in the SAS (ACPS) in patients with sneezing, coughing, Valsalva maneuver, and exercising effects in contrast to other patients. Moreover, ACPS reduction was not related to the intensity of the disease in both treatment methods. In contrast to shunt, an increase in the obstruction level in AS led to a reduction in ACPS in ETV in both CSF dynamic conditions. CONCLUSIONS: The noises from irregular disorders increased the discharging of CSF after shunt placement, and activities such as sneezing, coughing, Valsalva maneuvers, and exercising increased the risk of shunt overdrainage by 10.4~47.8%, especially in the patient with intracranial hypertension. Based on the proposed in vitro ETV and shunt models, an increase of head compliance was higher in ETV compared to the shunt. Eventually, an increase in the obstruction level of AS after ETV led to a decline in head compliance in contrast to shunt.