Particulate Matter and Its Molecular Effects on Skin: Implications for Various Skin Diseases.

Particulate matter (PM) is a harmful air pollutant composed of chemicals and metals which affects human health by penetrating both the respiratory system and skin, causing oxidative stress and inflammation. This review investigates the association between PM and skin disease, focusing on the underlying molecular mechanisms and specific disease pathways involved. Studies have shown that PM exposure is positively associated with skin diseases such as atopic dermatitis, psoriasis, acne, and skin aging. PM-induced oxidative stress damages lipids, proteins, and DNA, impairing cellular functions and triggering inflammatory responses through pathways like aryl hydrocarbon receptor (AhR), NF-κB, and MAPK. This leads to increased production of inflammatory cytokines and exacerbates skin conditions. PM exposure exacerbates AD by triggering inflammation and barrier disruption. It disrupts keratinocyte differentiation and increases pro-inflammatory cytokines in psoriasis. In acne, it increases sebum production and inflammatory biomarkers. It accelerates skin aging by degrading ECM proteins and increasing MMP-1 and COX2. In conclusion, PM compromises skin health by penetrating skin barriers, inducing oxidative stress and inflammation through mechanisms like ROS generation and activation of key pathways, leading to cellular damage, apoptosis, and autophagy. This highlights the need for protective measures and targeted treatments to mitigate PM-induced skin damage.

Needleless laser injector versus needle injection for skin enhancement and rejuvenation effect of dermal filler.

BACKGROUND AND OBJECTIVES: A needleless laser-induced microjet injector is a novel transdermal drug delivery system that can rapidly inject a very small and precise drug dose into the skin with minimal pain and downtime. In this study, we aimed to compare the laser-induced microjet injection versus needle injection of polylactic acid/hyaluronic acid filler for skin enhancement and rejuvenation. PATIENTS AND METHODS: A 24-week prospective, single-center, assessor-blinded, randomized, split-face study was conducted. The enrolled patients underwent one treatment session of dermal filler injection using a laser-induced microjet injector on one half of the face or a traditional needle injection on the other half of the face. Evaluation was conducted at baseline before treatment and at 4, 12, and 24 weeks after treatment. RESULTS: A single treatment of filler injection with a laser-induced microjet injector resulted in similar improvements in skin hydration and elasticity as a single treatment of filler injection by using manual needle injection, with reduced pain, side effects, and decreased treatment time. CONCLUSIONS: Laser-induced microjet injector enabled not only the application of a controlled dose and filler depth but also even distribution, improved clinical efficacy, reduced pain and side effects, and sufficient time for clinicians to perform treatment.

A Randomized Split-Face Study of Photodynamic Therapy With St. John's Wort and Indole-3-Acetic Acid for the Treatment of Acne.

BACKGROUND: St. John's wort (SJW) contains hypericin, a powerful photosensitizer with antimicrobial and anti-inflammatory activities. OBJECTIVE: To compare the efficacy and safety of SJW-photodynamic therapy (PDT) with that of indole-3-acetic acid (IAA)-PDT for the treatment of acne and investigate the skin rejuvenating effects of SJW-PDT. MATERIALS AND METHODS: In vitro experiments were conducted to examine the generation of reactive oxygen species and the antimicrobial effects of SJW-PDT. In the prospective, double-blind, split-face, randomized study, 31 patients with facial acne were treated with SJW or IAA with simultaneous illumination of red light and green light. RESULTS: SJW produces free radicals with visible light irradiation, and the growth of Cutibacterium acnes and Staphylococcus aureus is significantly suppressed. One week after the last treatment, the acne lesion counts were significantly decreased in both groups (56.5% reduction in SJW, p < .001 vs 57.0% in IAA, p < .001). Significant reductions in sebum secretion, erythema index, roughness, and wrinkles were observed in both groups after the treatment. No side effects were observed. CONCLUSION: SJW-PDT is a simple, safe, and effective treatment option for acne that is also beneficial for skin rejuvenation.

Efficacy and Safety of the Micro-insulated Needle Radiofrequency Device for Reduction of Submental Fat.

BACKGROUND: Recently, it has been reported that a micro-insulated needle radiofrequency (RF) system is effective at achieving subcutaneous fat reduction; however, no study has yet applied this technique to reduce submental fat. OBJECTIVE: To evaluate the efficacy and safety of a fractional RF device with a micro-insulated needle to reduce submental fat. MATERIALS AND METHODS: In this prospective, single-blinded, pre-post comparative study, 24 adults with excess submental fat were treated once using a micro-insulated needle RF device. Outcomes included efficacy (submental fat rating by an independent investigator, fat volume quantified with a 3-dimensional camera, and patient satisfaction), assessed 1 and 2 months after the procedure, and safety (adverse events), assessed throughout the study. RESULTS: The patients' Physician-Assisted Submental Fat Rating Scale score significantly decreased after 1 month and further decreased after 2 months. The average volume of submental fat was significantly decreased after 2 months (20.44 ± 5.53 cc to 16.41 ± 4.58 cc, p < .001). Patient satisfaction was high. Transient and mild local skin reactions without long-term sequelae were observed in 4 patients. CONCLUSION: The micro-insulated needle RF device is beneficial for the reduction of submental fat and has tolerable safety profiles. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05517824.

Clinical Implication of the Regional Thickness of the Lower Facial Skin, Superficial Fat, and Superficial Musculoaponeurotic System on High-Intensity Focused Ultrasound Treatment.

BACKGROUND: 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. OBJECTIVE: To demonstrate the topographic thickness of the lower facial skin, superficial fat, and SMAS. MATERIALS AND METHODS: The ultrasound data of 200 healthy patients who underwent lower facial rejuvenation were retrospectively reviewed. RESULTS: 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. CONCLUSION: 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.

Working memory deficits in patients with idiopathic restless legs syndrome are associated with abnormal theta-band neural synchrony.

Cognitive impairment, particularly prefrontal function, has been reported in patients with restless legs syndrome. However, working memory performance in patients with restless legs syndrome remains uncertain. The present study aimed to examine working memory performance in patients with restless legs syndrome by investigating electroencephalography theta-band oscillations within task-relevant brain regions and the synchronization among oscillations during a working memory task. Twelve female idiopathic patients with restless legs syndrome and 12 female healthy controls participated in this study. Nineteen-channel electroencephalography data were recorded while participants performed a Sternberg working memory task. We analysed event-related theta-band activity and interregional theta-band phase synchrony during the memory retrieval phase. The spatial pattern of theta-band phase synchrony was quantified using graph theory measures, including the clustering coefficient, characteristic path length, and small-world propensity. Considerable increases in theta-band activity and theta-band phase synchrony were observed at 600-700 ms in controls and at 650-750 ms in restless legs syndrome subjects after the probe item was presented. During this period, induced theta-band activity showed lower with borderline significance in the restless legs syndrome subjects than in the controls regardless of channel location (F4,88  = 3.92, p = .06). Theta-band phase synchrony between the frontal and posterior regions was significantly reduced in the restless legs syndrome subjects. Inefficiency in both global and local networks in the restless legs syndrome subjects was revealed by the decreased small-world propensity (t22  = 2.26, p = .03). Small-world propensity was negatively correlated with restless legs syndrome severity (r = -.65, p = .02). Our findings suggest that patients with restless legs syndrome have multiple deficits in cognitive processes, including attentional allocation, evaluation of incoming stimuli, and memory manipulation of encoded information during a working memory task. Abnormal local theta-band neural synchrony and global theta-band neural synchrony may underlie the neurophysiological mechanism of the working memory dysfunction associated with restless legs syndrome.

The long-term risk of lymphoma and skin cancer did not increase after topical calcineurin inhibitor use and phototherapy in a cohort of 25,694 patients with vitiligo.

BACKGROUND: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. OBJECTIVE: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. METHODS: A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. RESULTS: During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. LIMITATIONS: Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. CONCLUSION: The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

Resveratrol Inhibits Particulate Matter-Induced Inflammatory Responses in Human Keratinocytes.

Particulate matter (PM), a major air pollutant, is a complex mixture of solid and liquid particles of various sizes. PM has been demonstrated to cause intracellular inflammation in human keratinocytes, and is associated with various skin disorders, including atopic dermatitis, eczema, and skin aging. Resveratrol is a natural polyphenol with strong antioxidant properties, and its beneficial effects against skin changes due to PM remain elusive. Therefore, in the present study, we investigated the effect of resveratrol on PM-induced skin inflammation and attempted to deduce the molecular mechanisms underlying resveratrol's effects. We found that resveratrol inhibited PM-induced aryl hydrocarbon receptor activation and reactive oxygen species formation in keratinocytes. It also suppressed the subsequent cellular inflammatory response by inhibiting mitogen-activated protein kinase activation. Consequentially, resveratrol reduced PM-induced cyclooxygenase-2/prostaglandin E2 and proinflammatory cytokine expression, including that of matrix metalloproteinase (MMP)-1, MMP-9, and interleukin-8, all of which are known to be central mediators of various inflammatory conditions and aging. In conclusion, resveratrol inhibits the PM-induced inflammatory response in human keratinocytes, and we suggest that resveratrol may have potential for preventing air pollution-related skin problems.

A First-in-Human Phase I Study of GC1118, a Novel Anti-Epidermal Growth Factor Receptor Antibody, in Patients with Advanced Solid Tumors.

LESSONS LEARNED: GC1118 is a novel fully human anti-epidermal growth factor receptor (EGFR) antibody with unique binding epitopes and different ligand-binding inhibitory activity compared with cetuximab or panitumumab.GC1118 showed promising antitumor activity, especially in patients with colorectal cancer resistant to prior EGFR antibody. Skin toxicities were more common and diarrhea was less frequent compared with other anti-EGFR antibodies. BACKGROUND: GC1118 is a novel monoclonal antibody targeting epidermal growth factor receptor (EGFR) with more potent ligand inhibition than cetuximab or panitumumab. We conducted a first-in-human, phase I study of GC118 in patients with refractory solid tumors. METHODS: In the dose escalation part, GC1118 was administered on days 1, 8, 15, and 22, followed by a 2-week rest, during which dose-limiting toxicities (DLTs) were evaluated. In the expansion part, patients were enrolled into three cohorts (Cohort 1 [C1], patients with colorectal cancer [CRC] without prior anti-EGFR treatment; Cohort 2 [C2], patients with CRC with tumors resistant to anti-EGFR therapy; Cohort 3 [C3], EGFR-overexpressing gastric cancer). RESULTS: In the dose escalation part, 24 patients were treated at five dose levels: 0.3, 1.0, 3.0, 4.0, and 5.0 mg/kg. In the 5.0 mg/kg cohort, two patients experienced DLTs (skin toxicities). The maximum-tolerated dose (MTD) was 4.0 mg/kg. Common adverse events were skin toxicities. In the expansion part, 39 patients were enrolled. In Cohort 1, stable disease (SD) was observed in 58%; in Cohort 2, partial response (PR) 17% and SD 8%; in Cohort 3, PR 8% and SD 17%. CONCLUSION: GC1118 showed promising antitumor activity and was well tolerated. Infrequent diarrhea compared with other anti-EGFR antibodies might be advantageous for further development.

Comparison of the Treatment Outcome of Oral Tofacitinib with Other Conventional Therapies in Refractory Alopecia Totalis and Universalis: A Retrospective Study.

Treatment of alopecia totalis and alopecia universalis is often challenging and unsatisfactory. Recently, Janus kinase inhibitor has shown promising results. The aim of this study is to compare the efficacy and tolerability of oral tofacitinib and conventional modalities for treating refractory alopecia totalis/universalis. A total of 74 patients (18 treated with tofacitinib, 26 treated with conventional oral treatment (steroid ± cyclosporine), and 30 treated with diphenylcyclopropenone) were included in the study. The patients' medical records were reviewed retrospectively. After 6 months, 44.4% of patients in the tofacitinib group, 37.5% in the conventional oral treatment group, and 11.1% in the diphenylcyclopropenone group achieved 50% improvements in the Severity of Alopecia Tool score. During treatment, 10% of patients in the tofacitinib group, 73.1% in the conventional oral treatment group, and 10% in the diphenylcyclopropenone group experienced adverse drug reactions. In conclusion, oral tofacitinib was more effective than diphenylcyclopropenone immunotherapy and more tolerable than conventional oral treatment after 6 months of treatment.

Changes in Lesional and Non-lesional Skin Microbiome During Treatment of Atopic Dermatitis.

The aim of this study was to evaluate changes in the skin surface microbiome in patients with atopic dermatitis during treatment. The effect of narrowband ultraviolet B phototherapy was also studied to determine the influence of exposure to ultraviolet. A total of 18 patients with atopic dermatitis were included in the study. Patients were divided into 2 groups based on treatment: 1 group treated with narrowband ultraviolet B phototherapy and topical corticosteroid, and the other group treated with topical corticosteroid only. Skin swabs and high-throughput sequencing of 16S ribosomal RNA bacterial genes were performed at 3 time-points. The microbial diversity of lesional skin increased greatly after treatment. The proportion of Staphylococcus aureus showed a significant positive correlation with eczema severity. In conclusion, a drastic increase in microbial diversity and decrease in S. aureus proportion were observed with eczema treatment. Narrowband ultraviolet B treatment did not exert additive effects on eczema improvement; however, it appeared to reduce the recurrence of eczema.

Comparison of Surgical Outcomes of Rectangular Lid Excision Versus Elliptical Excision for the Treatment of Epidermal Cysts.

BACKGROUND: Elliptical excision (EE) has been the standard surgical technique for the removal of epidermal cysts. However, it produces to create a long, linear wound causing cosmetic concerns. OBJECTIVE: The purpose of the study was to evaluate the cosmetic outcomes and postoperative complications of rectangular lid excision (LE) compared with EE in epidermal cyst removals. METHODS: Medical records of patients who received surgical excision for epidermal cysts were retrospectively reviewed. Three dermatologists evaluated the postoperative photographs using 4-scale investigator's global assessment. RESULTS: Of the 123 lesions, EE and LE were performed in 58 and 65 lesions, respectively. Although the mean diameter of cysts was significantly greater in the LE group than in the EE group, the number of postoperative complications was not different between the 2 groups. A photographic assessment was performed in 11 lesions in the LE group and 11 lesions in the EE group. Although the mean diameter of cysts was greater in the LE group than in the EE group, the cosmetic outcome was significantly better in the LE group. CONCLUSION: The LE technique was shown to have a superior cosmetic outcome than the EE technique. Hence, it is a viable alternative for the removal of epidermal cysts.

Resveratrol as a Multifunctional Topical Hypopigmenting Agent.

Melanin is produced in melanocytes and stored in melanosomes, after which it is transferred to keratinocytes and, thus, determines skin color. Despite its beneficial sun-protective effects, abnormal accumulation of melanin results in esthetic problems. A range of topical hypopigmenting agents have been evaluated for their use in the treatment of pigmentary disorders with varying degrees of success. Hydroquinone (HQ), which competes with tyrosine, is the main ingredient in topical pharmacological agents. However, frequent occurrence of adverse reactions is an important factor that limits its use. Thus, efforts to discover effective topical hypopigmenting agents with less adverse effects continue. Here, we describe the potential of resveratrol to function as an effective hypopigmenting agent based on its mechanism of action. Resveratrol is not only a direct tyrosinase inhibitor but an indirect inhibitor as well. Additionally, it can affect keratinocytes, which regulate the function of melanocytes. Resveratrol regulates the inflammatory process of keratinocytes and protects them from oxidative damage. In this way, it prevents keratinocyte-induced melanocyte stimulation. Furthermore, it has a rescuing effect on the stemness of interfollicular epidermal cells that can repair signs of photoaging in the melasma, a typical pigmentary skin disorder. Overall, resveratrol is a promising potent hypopigmenting agent.

Molecular Mechanisms of Dermal Aging and Antiaging Approaches.

The dermis is primarily composed of the extracellular matrix (ECM) and fibroblasts. During the aging process, the dermis undergoes significant changes. Collagen, which is a major component of ECM, becomes fragmented and coarsely distributed, and its total amount decreases. This is mainly due to increased activity of matrix metalloproteinases, and impaired transforming growth factor-ß signaling induced by reactive oxygen species generated during aging. The reduction in the amount of collagen hinders the mechanical interaction between fibroblasts and the ECM, and consequently leads to the deterioration of fibroblast function and further decrease in the amount of dermal collagen. Other ECM components, including elastic fibers, glycosaminglycans (GAGs), and proteoglycans (PGs), also change during aging, ultimately leading to a reduction in the amount of functional components. Elastic fibers decrease in intrinsically aged skin, but accumulate abnormally in photoaged skin. The changes in the levels of GAGs and PGs are highly diverse, and previous studies have reported conflicting results. A reduction in the levels of functional dermal components results in the emergence of clinical aging features, such as wrinkles and reduced elasticity. Various antiaging approaches, including topicals, energy-based procedures, and dermal fillers, can restore the molecular features of dermal aging with clinical efficacy. This review summarizes the current understanding of skin aging at the molecular level, and associated treatments, to put some of the new antiaging technology that has emerged in this rapidly expanding field into molecular context.

The efficacy of micro-insulated needle radiofrequency system for the treatment of lower eyelid fat bulging.

BACKGROUND AND OBJECTIVES: Conventional treatment options for eyelid fat bulging are generally limited to surgical approaches. However, many attempts have been made recently to manage this disfigurement using non-surgical interventions. The purpose of this study was to evaluate the efficacy and safety of a micro-insulated needle radiofrequency system for the treatment of lower eyelid fat bulging. METHODS: This is a single center pre-post comparative study. Twenty-two subjects with lower eyelid fat bulging were treated twice using the needle radiofrequency system, at an interval of four weeks. Two types of partially insulated needles with different lengths were used in each session. A three-dimensional photogrammetry system was used to objectively measure changes in the extent of the fat bulge. The investigator's global assessment (IGA) of the severity of fat bulging was also evaluated. RESULTS: The average extent of fat bulging was decreased significantly after twelve weeks, and was maintained until 24 weeks. The IGA score was significantly decreased after four weeks and further decreased after twelve weeks, and then maintained until 24 weeks. There were no side effects, except for lower eyelid swelling and bruising that lasted for about a week. CONCLUSION: The micro-insulated needle radiofrequency system can be a beneficial and well-tolerated treatment for lower eyelid fat bulging.

Rational Design of in Vivo Tau Tangle-Selective Near-Infrared Fluorophores: Expanding the BODIPY Universe.

The elucidation of the cause of Alzheimer's disease remains one of the greatest questions in neurodegenerative research. The lack of highly reliable low-cost sensors to study the structural changes in key proteins during the progression of the disease is a contributing factor to this lack of insight. In the current work, we describe the rational design and synthesis of two fluorescent BODIPY-based probes, named Tau 1 and Tau 2. The probes were evaluated on the molecular surface formed by a fibril of the PHF6 (306VQIVYK311) tau fragment using molecular docking studies to provide a potential molecular model to rationalize the selectivity of the new probes as compared to a homologous Aß-selective probe. The probes were synthesized in a few steps from commercially available starting products and could thus prove to be highly cost-effective. We demonstrated the excellent photophysical properties of the dyes, such as a large Stokes shift and emission in the near-infrared window of the electromagnetic spectrum. The probes demonstrated a high selectivity for self-assembled microtubule-associated protein tau (Tau protein), in both solution and cell-based experiments. Moreover, the administration to an acute murine model of tauopathy clearly revealed the staining of self-assembled hyperphosphorylated tau protein in pathologically relevant hippocampal brain regions. Tau 1 demonstrated efficient blood-brain barrier penetrability and demonstrated a clear selectivity for tau tangles over Aß plaques, as well as the capacity for in vivo imaging in a transgenic mouse model. The current work could open up avenues for the cost-effective monitoring of the tau protein aggregation state in animal models as well as tissue staining. Furthermore, these fluorophores could serve as the basis for the development of clinically relevant sensors, for example based on PET imaging.

The Co-Expression Pattern of p63 and HDAC1: A Potential Way to Disclose Stem Cells in Interfollicular Epidermis.

Stem cell markers of interfollicular epidermis (IEF) have not been established thus far. The aim of this study is to suggest a new way to disclose IFE-stem cells by combining the expression of histone deacetylases (HDAC) 1 and p63. Immunohistochemical staining of HDAC1 and p63 was performed in six normal human samples. Moreover, a skin equivalent (SE) model was treated with suberoylanilohydroxamic acid (SAHA, an HDAC inhibitor) to elucidate the role of HDAC1. Finally, rapidly adhering (RA) keratinocytes to a type IV collagen, which have been identified to represent epidermal stem cells, were subjected to Western blot analysis with antibodies against HDAC1. In normal samples, there was a minor subpopulation comprised of p63-positive and HDAC1-negative cells in the basal layers. The proportion of this subpopulation was decreased with age. In the SE model, SAHA treatment increased the epidermal thickness and number of p63-positive cells in a dose dependent manner. After SAHA treatment, the expression of differentiation markers was decreased, while that of basement membrane markers was increased. In a Western blot analysis, HDAC1 was not expressed in RA cells. In conclusion, the combination of p63-positive and HDAC1-negative expressions can be a potential new way for distinguishing epidermal stem cells.

Ginsenoside Rg3 Improves Recovery from Spinal Cord Injury in Rats via Suppression of Neuronal Apoptosis, Pro-Inflammatory Mediators, and Microglial Activation.

Spinal cord injury (SCI) is one of the most devastating medical conditions; however, currently, there are no effective pharmacological interventions for SCI. Ginsenoside Rg3 (GRg3) is one of the protopanaxadiols that show anti-inflammatory, anti-oxidant, and neuroprotective effects. The present study investigated the neuroprotective effect of GRg3 following SCI in rats. SCI was induced using a static compression model at vertebral thoracic level 10 for 5 min. GRg3 was administrated orally at a dose of 10 or 30 mg/kg/day for 14 days after the SCI. GRg3 (30 mg/kg) treatment markedly improved behavioral motor functions, restored lesion size, preserved motor neurons in the spinal tissue, reduced Bax expression and number of TUNEL-positive cells, and suppressed mRNA expression of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6. GRg3 also attenuated the over-production of cyclooxygenase-2 and inducible nitric oxide synthase after SCI. Moreover, GRg3 markedly suppressed microglial activation in the spinal tissue. In conclusion, GRg3 treatment led to a remarkable recovery of motor function and a reduction in spinal tissue damage by suppressing neuronal apoptosis and inflammatory responses after SCI. These results suggest that GRg3 may be a potential therapeutic agent for the treatment of SCI.