Promoting epidermal cell survival in an oxidative stress microenvironment is vital for skin regeneration after burns and/or wounds. However, few studies have explored the mediators related to epidermal cell apoptosis in an oxidative stress microenvironment. Cellular viability was determined using the MTT assay, TUNEL staining, western blot analysis and LDH release assay. Two independent siRNAs were transfected into HaCaT cell to repress INF2 and/or HIF1 in the presence of H2O2. Mitochondrial function was determined using JC-1 staining, mitochondrial ROS staining, immunofluorescence staining and western blotting. In the present study, our data demonstrated that the expression of inverted formin-2 (INF2) increased rapidly when the cells were exposed to H2O2. Interestingly, INF2 knockdown promoted HaCaT cell survival via reducing H2O2-mediated cell apoptosis. Molecular investigations demonstrated that INF2 deletion attenuated mitochondrial ROS overloading, restored the cellular redox balance, sustained the mitochondrial membrane potential, improved mitochondrial respiratory function and corrected the mitochondrial dynamics disorder in an H2O2-mimicking oxidative stress microenvironment. In addition, INF2 deletion upregulated the expression of HIF1. Interestingly, the inhibition of HIF1 increased cell death and caused mitochondrial stress despite the deletion of INF2, suggesting that the HIF1 signaling pathway is required for INF2 deletion-mediated HaCaT cell survival and mitochondrial protection. Altogether, our results identified INF2 as a novel apoptotic mediator for oxidative stress-mediated HaCaT cell death via modulating mitochondrial stress and repressing the HIF1 signaling pathway. This finding provides evidence to support the critical role played by the INF2-HIF1 axis in regulating mitochondrial stress and epidermal cell viability in an oxidative stress microenvironment.

Background: With the growth in the popularity of facial filler injections, increased numbers of severe adverse events, such as cerebral embolism, have been reported. Objectives: The aim of this article was to summarize the clinical manifestations and proposed mechanisms of filler-induced cerebral embolism (FICE). Methods: A literature review was performed with the search keywords “filler injection,” “hyaluronic acid,” “fat graft,” “cerebral infarction,” “cerebral embolism,” “stroke,” “cerebrovascular infarction,” “disorders of consciousness,” and “hemiplegia.” Results: Among the 43 cases of FICE enrolled from 35 articles, 37 patients were female, and 6 were male. Twenty-nine of these patients had received fat grafting, and 12 hyaluronic acid injection. Most FICE patients had been injected in the glabella, followed by the temporal, forehead, and nasal areas. Among 30 patients injected under local anesthesia, 43.33% presented with neurologic symptoms during the procedure. The main symptoms were consciousness disorders and hemiplegia. Most of the embolization sites were in the middle cerebral artery, followed by frontal lobe infarction and anterior cerebral artery infarction. Three patients developed cerebral hemorrhage after embolism. Twenty-six patients presented with newly acquired vision loss. The management for FICE cases included embolectomy, thrombolysis, decompressive craniectomy, antiplatelet/anticoagulant therapy, and symptomatic and nutritional treatment. Nearly half of the patients recovered or exhibited improved neurologic manifestations but not visual loss. Five patients died. Conclusions: FICE is a severe complication following facial filler injection. Careful prevention, timely identification, and treatment are crucial to decreasing the morbidity and mortality of FICE. Level of Evidence: 4:

In patients with localized scleroderma (LoS), facial deformity induced by subcutaneous atrophy greatly reduces life quality. Autologous fat grafting (AFG) is used for volume restoration but with low-fat retention due to various reasons. Adipose-derived stem cells (ADSCs) have shown potential effects in improving fat retention. We aimed to compare the feasibility and efficacy of improving fat retention in LoS patients among the ADSCs-assisted, the stromal vascular fraction (SVF)-assisted and conventional AFG methods. A pilot study with a 6-month follow-up among 18 LoS patients was conducted. Participants were randomly assigned into three AFG groups: conventional group, SVF-assisted group, and ADSCs-assisted group. The SVF-assisted group received SVF-assisted AFG at the SVF:fat ratio of 1:1. The ADSCs-assisted group received the mixture of ADSCs-enriched fat graft supplemented with 5 × 105 ADSCs/mL fat. Volume retention was measured by magnetic resonance imaging, and clinical photographs were taken for outcome evaluation. At sixth-month follow-up, the fat retention of ADSCs-assisted group was 49.83 ± 3.61%, significantly higher than 31.75 ± 1.73% of SVF-assisted group (P = .0004), and 21.86 ± 1.68% of the conventional group (P < .0001). A significant difference of the fat retention was also observed between the SVF-assisted and conventional group (P = .0346). No severe adverse events occurred during the procedure and follow-up. This pilot study suggests that ADSCs-assisted AFG is a safe, feasible, and attractive alternative to conventional and SVF-assisted AFG in the correction of facial atrophy of LoS patients. Future studies with large patient samples are needed for confirmation. (Chinese Clinical Trial Registry, ChiCTR1900025717).

Background: The morning blood pressure surge (MBPS) is related to an exaggerated risk of cardiovascular diseases and mortality. With increasing attention on circadian change in blood pressure and extensive use of ambulatory blood pressure monitoring (ABPM), chronotherapy that administration of medication according to biological rhythm, is reported to improve cardiovascular outcomes. The aim of this study is to evaluate the influence of chronotherapy of antihypertensive drugs upon MBPS in hypertensive patients.Methods: A search strategy was applied in Ovid MEDLINE, EMBASE, Cochrane (Wiley) CENTRAL Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the Chinese Biomedical literature database. No language and date restrictions. Randomized controlled trials (RCT) assessing the efficacy of evening and morning administration of the same medications in adult patients with primary hypertension were included.Results: A total of ten trials, comprising 1724 participants with a mean age of 61 and 51% female, were included in this study. Combined analysis observed significant reduction of MBPS (− 5.30 mmHg, 95% CI − 8.80 to − 1.80), night-time SBP (− 2.29 mmHg, 95% CI − 4.43 to − 0.15), night-time DBP (− 1.63 mmHg, 95 %CI − 3.23 to − 0.04) and increase in night blood pressure dipping (3.23%, 95% CI 5.37 to 1.10) in evening dosage compared with traditional morning dosage of blood pressure-lowering drugs. No significant difference was found in the incidence of overall adverse effects (RR 0.65, 95% CI 0.30 to 1.41) and withdrawal due to adverse effects (RR 0.95, 95% CI 0.53 to 1.71).Conclusions: Our study suggested that evening administration of antihypertensive medications exerted better blood pressure-lowering effect on MBPS compared with conventional morning dosage. Safety assessment also indicated that the evening regimen did not increase the risk of adverse events. However, endpoint studies need to be carried out to confirm the significance and feasibility of this treatment regimen in clinical practice.