Although the pathogenesis of solar lentigo (SL) involves chronic ultraviolet (UV) exposure, cellular senescence, and upregulated melanogenesis, underlying molecular-level mechanisms associated with ...SL remain unclear. The aim of this study was to investigate the gene regulatory mechanisms intimately linked to inflammation in SL. Skin samples from patients with SL with or without histological inflammatory features were obtained. RNA-seq data from the samples were analyzed via multiple analysis approaches, including exploration of core inflammatory gene alterations, identifying functional pathways at both transcription and protein levels, comparison of inflammatory module (gene clusters) activation levels, and analyzing correlations between modules. These analyses disclosed specific core genes implicated in oxidative stress, especially the upregulation of nuclear factor kappa B in the inflammatory SLs, while genes associated with protective mechanisms, such as SLC6A9, were highly expressed in the non-inflammatory SLs. For inflammatory modules, Extracellular Immunity and Mitochondrial Innate Immunity were exclusively upregulated in the inflammatory SL. Analysis of protein-protein interactions revealed the significance of CXCR3 upregulation in the pathogenesis of inflammatory SL. In conclusion, the upregulation of stress response-associated genes and inflammatory pathways in response to UV-induced oxidative stress implies their involvement in the pathogenesis of inflammatory SL.
Leucine‐rich repeat LGI family member 3 (LGI3), a member of the LGI family, is a secreted protein that is expressed not only in the brain and adipose tissues, but also in various skin cells. We ...previously reported that LGI3 was secreted after exposure to ultraviolet B and promoted the migration of HaCaT human keratinocytes. In the present study, we investigated whether LGI3 influences the differentiation of keratinocytes. The results show that the expression of involucrin, a keratinocyte differentiation marker, was reduced in tissue from LGI3‐knockout mice. Those results indicate that LGI3 plays an important role in keratinocyte differentiation. Therefore, we treated HaCaT cells with LGI3 to examine its effect on keratinocyte differentiation. Protein levels of various differentiation markers were enhanced by treatment with LGI3. Furthermore, expression of differentiation markers was inhibited when keratinocytes were transfected with an siRNA for LGI3. LGI3 strongly activated Akt, whereas it had no apparent effect on extracellular signal‐regulated kinase, p38 mitogen‐activated protein kinase, or the c‐Jun N‐terminal kinase. A specific inhibitor of phosphoinositide 3‐kinase, LY294002, reduced LGI3‐induced expression of differentiation markers in HaCaT cells. Taken together, these results suggest that LGI3 promotes keratinocyte differentiation and could be used as a therapeutic agent to recover skin barrier function in epidermal barrier disruption.
Background
Extracellular matrix (ECM) components promote the development of skin wounds by providing biological scaffolds and regenerative microenvironments.
Aims
To evaluate the beneficial effects ...of human dermal fibroblast‐derived ECM after fractional carbon dioxide laser resurfacing in Asians.
Patients/Methods
In this double‐blind, randomized, vehicle‐controlled, split‐face study, 15 participants with features of facial skin aging were treated with a single session of fractional carbon dioxide laser, followed by the application of either ECM (ECM group) or placebo (control group). In vivo skin parameters were measured at baseline and after 4 and 12 weeks of treatment using the Antera 3D®, Cutometer® MPA580, Dermascan®, and Tewameter®.
Results
A total of 14 participants (mean age 45.1 ± 9.7 years) completed the study. The change in melanin level was significantly lower in the ECM group than in the control group at week 12 (p < 0.05). Transient increase in erythema level was observed at week 4 in the control group, and the change in the erythema level was greater in the control group than in the ECM group (p = 0.014). Though the ECM group showed improvements in the dermal density, texture, transepidermal water loss, marionette lines (volume, maximum depth, and average depth), and nasolabial folds (volume, maximum depth, and length), no significant differences were found between the two groups. Treatment‐related adverse events were not reported.
Conclusions
We suggest that human dermal fibroblast‐derived ECM may be used as adjunctive therapy after fractional carbon dioxide resurfacing to prevent postinflammatory hyperpigmentation in Asians.
Diabetic nephropathy (DN) is associated with high risk of cardiovascular disease and mortality. Exosomal microRNAs (miRNAs) regulate gene expression in a variety of tissues and play important roles ...in the pathology of various diseases. We hypothesized that the exosomal miRNA profile would differ between DN patients and patients without nephropathy.
We prospectively enrolled 74 participants, including healthy volunteers (HVs), diabetic patients without nephropathy, and those with DN. The serum exosomal miRNA profiles of participants were examined using RNA sequencing.
The expression levels of 107 miRNAs differed between HVs and patients without DN, whereas the expression levels of 95 miRNAs differed between HVs and patients with DN. Among these miRNAs, we found 7 miRNAs (miR-1246, miR-642a-3p, let-7c-5p, miR-1255b-5p, let-7i-3p, miR-5010-5p, miR-150-3p) that were uniquely up-regulated in DN patients compared to HVs, and miR-4449 that was highly expressed in DN patients compared to patients without DN. A pathway analysis revealed that these eight miRNAs are likely involved in MAPK signaling, integrin function in angiogenesis, and regulation of the AP-1 transcription factor. Moreover, they were all significantly correlated with the degree of albuminuria.
Patients with DN have a different serum exosomal miRNA profile compared to HVs. These miRNAs may be promising candidates for the diagnosis and treatment of DN and cardiovascular disease.
The time at which hypertension treatment should be initiated for different age groups and sexes remains controversial. We aimed to determine whether the association between blood pressure (BP) and ...major adverse cardiovascular events (MACE) varies with age and sex. This study enrolled 327,328 subjects who had not taken antihypertensive medication in the Korean National Health Service-National Health Screening Cohort between 2002 and 2003. Participants were categorized into four groups according to 2017 American College of Cardiology/American Heart Association hypertension guideline. Primary outcome was MACE characterized by cardiovascular mortality, myocardial infarction, unstable angina, and stroke. During a 10-year follow-up, a significant increase in MACE risk was observed from the stage 1 hypertension group (hazard ratio HR, 1.23; 95% CI 1.15-1.32; P < 0.001) in time-varying Cox analysis. This relationship was persistent in subjects aged < 70 years, but increased MACE risk was observed only in the stage 2 hypertension group in ≥ 70 years (HR, 1.52; 95% CI 1.32-1.76, P < 0.001). When categorized as per sex, both men and women showed significant MACE risk from stage 1 hypertension. However, on comparing the sexes after stratifying by age, a significantly increased risk of MACE was shown from stage 1 hypertension in men aged < 50 years, but from stage 2 hypertension in men aged ≥ 50 years. Meanwhile, increased MACE risk was observed from stage 2 hypertension in women aged < 60 years, but from stage 1 hypertension in women aged ≥ 60 years. Thus, young male subjects had higher MACE risk than young female subjects, but this difference gradually decreased with age and there was no difference between sexes in subjects aged ≥ 70 years. Therefore, our results suggest that hypertension treatment initiation may need to be individualized depending on age and sex.
Knowledge of the topographic thickness of the skin and soft tissues is necessary when performing a high-intensity focused ultrasound (HIFU) procedure. Thermal tissue injury to the superficial ...musculoaponeurotic system (SMAS) or deeper can injure the facial nerve and its branches.
To demonstrate the topographic thickness of the lower facial skin, superficial fat, and SMAS.
The ultrasound data of 200 healthy patients who underwent lower facial rejuvenation were retrospectively reviewed.
The mean age was 41.1 ± 13.7 years (range, 19-76 years). The jowl had thinner skin, thicker superficial fat, and deeper superficial and deep margins of the SMAS than the preauricle or lower cheek. The thickness of the superficial fat decreased with age, especially on the preauricle, lower cheek, and jowl. Women had thicker superficial fat than men on the preauricle and lower cheek. The superficial and deep margins of the SMAS were located more superficially in old and male patients with a slim facial figure than in young and female patients with a chubby facial figure.
The present findings provide anatomical information regarding the superficial fat and SMAS, which is useful in determining the focal penetration depth of HIFU treatment for lower face rejuvenation.
Treatment of periorbital wrinkles is a challenging task because of its anatomical significance and delicate nature.
The aim of this study was to evaluate the efficacy and safety of a microneedle ...monopolar radiofrequency (RF) device for treating periorbital wrinkles.
This retrospective study involved 21 patients who were treated for periorbital wrinkles using a RF device. The type of microneedle used, clinical photography, VISIA wrinkle score, and adverse events were collected from the medical chart. Two independent dermatologists assessed the photographs.
There were 18 female and 3 male patients with a mean age of 50.24 years. The severity of wrinkle was improved according to photographic assessment and VISIA wrinkle score at 6-month post-treatment. When 21 sites treated with a long microneedle (LMN, 1.5 mm) and the other 21 sites treated with a short microneedle (SMN, 0.8 mm) were compared, significant improvement in the VISIA wrinkle score was observed only in those treated with the LMN. No serious adverse events, including scarring and postinflammatory hyperpigmentation, occurred.
We demonstrated the efficacy and safety of the microneedle monopolar RF device in treating periorbital wrinkles. The LMN was superior to the SMN in reducing VISIA wrinkle score.
PDF
