ABSTRACT
Observational studies have suggested an associations between hidradenitis suppurativa (HS) and metabolic syndrome (MetS) and its components. However, it remains unclear whether the relationship is causal or not. Our study aimed to investigate the causal association of HS with MetS and its components. We performed a bidirectional, two-sample Mendelian randomization study using summary-level data from the most comprehensive genome-wide association studies of HS (n = 362 071), MetS (n = 291 107), waist circumference (n = 462 166), hypertension (n = 463 010) fasting blood glucose (FBG, n = 200 622), triglycerides (n = 441 016), and high-density lipoprotein cholesterol (HDL-C, n = 403 943). Genetic instrumental variables were constructed by identifying single nucleotide polymorphisms associated with the corresponding factors. The random-effects inverse-variance weighted method was applied as the primary method. The results showed that genetically predicted HS was positively associated with waist circumference risk in both directions. High waist circumference increased the risk of HS (odds ratio [OR] 4.147; 95% confidence interval [CI] 2.610-6.590; p = 1.746 × 10-9). In addition, HS was also affected by waist circumference (OR 1.009; 95% CI 1.006-1.012; p = 3.08 × 10-7). No causal relationships were found between HS and MetS or its components other than waist circumference. The findings highlight the importance of early intervention for obesity in HS patients. Further studies are needed to determine the pathophysiology of HS associated with MetS and its components.
ABSTRACT
INTRODUCTION: Pulsed dye laser (PDL) is currently considered to be the first-line treatment for port-wine stains (PWSs) on the extremities despite its less than satisfactory therapeutic efficacy. Hemoporfin-mediated photodynamic therapy (HMME-PDT) is a vascular-targeted therapy that has rarely been used to treat PWSs on the extremities. Here, we evaluate the clinical efficacy and safety of HMME-PDT for the treatment of PWSs on the extremities. METHODS: Clinical data and dermoscopic images of PWSs on the extremities were obtained from 65 patients who underwent HMME-PDT between February 2019 and December 2022. The clinical efficacy of HMME-PDT was analyzed by comparing the pre- and post-treatment images. The safety of HMME-PDT was evaluated through observation during the treatment period and post-treatment follow-up. RESULTS: The efficacy rate of a single HMME-PDT session was 63.0% and that of two and three to six sessions was 86.7% and 91.3%, respectively. A positive correlation was found between therapeutic efficacy and the number of HMME-PDT sessions. The therapeutic efficacy of HMME-PDT was better on the proximal extremities than on other parts of the extremities (P = 0.038), and the efficacy of treating PWSs in each site was relatively improved with an increase of treatment time. The clinical efficacy of HMME-PDT differed across four PWS vascular patterns identified by dermoscopy (P = 0.019). However, there was no statistical difference in the therapeutic efficacy based on age, sex, type of PWS, and treatment history (P > 0.05), which may be partly attributed to the relatively small sample size or poor cooperation of infant patients. No obvious adverse reactions were observed during the follow-up period. CONCLUSIONS: HMME-PDT is a very safe and effective treatment for PWSs on the extremities. Multiple HMME-PDT treatments, lesions located in proximal limbs, and PWSs with type I and IV vascular patterns under dermoscopy were associated with higher efficacy of HMME-PDT. Dermoscopy may help predict the clinical efficacy of HMME-PDT. TRIAL REGISTRATION NO: 2020KJT085.
ABSTRACT
BACKGROUND: Hemoporfin-mediated photodynamic therapy (Hemoporfin-PDT) has been approved for port-wine stain (PWS) in China in 2017. This study evaluated the efficacy and safety of Hemoporfin-PDT for PWS in a real life setting and investigated factors that influence the efficacy. METHODS: A multicenter retrospective study included patients with PWS who underwent Hemoporfin-PDT in 29 hospitals across China and completed at least two months of follow-up. The efficacy was evaluated based on patien photographs. RESULTS: A total of 1679 patients were included. After the first and second sessions of Hemoporfin-PDT, 63.5 and 75.3% of patients responded, respectively. The response rate of purple-type PWS was significantly lower than that of pink-type PWS (OR: 0.71, 95% CI: 0.54-0.94, P < 0.05), and there was no significant difference between thick- and pink-type (OR: 0.72, 95% CI: 0.42-1.22, P > 0.05). The response rate of PWS on the limbs was significantly lower than that on the mid-face (OR: 0.35, 95% CI: 0.23-0.53, P < 0.0001), while no significant difference was observed between PWS on the peripheral part of the face, neck or other parts of the body and PWS on the mid-face (P > 0.05). The response rate was lower in male patients with an age > 3 years or ≤ 6 years (P < 0.05). Previous treatment history did not affect the efficacy (P > 0.05). Hemoporfin-PDT was well tolerated. CONCLUSION: Patients with PWS have a good response and good tolerance to Hemoporfin-PDT.
Subject(s)
Photochemotherapy , Port-Wine Stain , Humans , Male , Child, Preschool , Photochemotherapy/methods , Port-Wine Stain/drug therapy , Photosensitizing Agents/therapeutic use , Retrospective Studies , HematoporphyrinsSubject(s)
Antineoplastic Agents , Gastrointestinal Neoplasms , Gastrointestinal Stromal Tumors , Panniculitis , Triazines , Humans , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/pathology , Pyrazoles/therapeutic use , Pyrroles/adverse effects , Panniculitis/chemically induced , Mutation , Protein Kinase Inhibitors/adverse effects , Antineoplastic Agents/adverse effects , Receptor, Platelet-Derived Growth Factor alpha/genetics , Receptor, Platelet-Derived Growth Factor alpha/therapeutic useABSTRACT
Background: Hemoporfin-mediated photodynamic therapy (HMME-PDT) is reported to be effective and safe for port-wine stains (PWS). However, its efficacy is influenced by several factors and there is no appropriate method to evaluate efficacy so far. Therefore, this study explored the clinical efficacy of HMME-PDT for PWS on the face and neck and the feasibility of evaluating treatment potency with optical coherence tomography (OCT). Methods: A total of 211 PWS patients subjected to HMME-PDT were recruited for study and correlations of therapeutic effect with treatment sessions, age, gender, lesion distribution and treatment history analyzed. OCT was utilized for quantitative analysis of PWS lesions of 36 selected patients before and after HMME-PDT. Results: The efficacy of two consecutive treatments was significantly higher than that of single treatment (P < 0.05). In multivariate analysis, after the first treatment, age, lesion distribution and treatment history were correlative factors affecting treatment efficacy (P < 0.05). The improvement effect on central facial lesions was lower than that on lateral facial lesions (P < 0.05). The efficacy of therapy on the group with no history of pulsed dye laser (PDL) treatment was greater than that on effective and ineffective treatment groups (P < 0.05). After the second session, age remained the only factor correlated with efficacy (P < 0.05). Dilated vessel diameter and depth before and after treatment were significantly different (P < 0.05). With increasing treatment times, age was the most significant factor influencing treatment efficacy. Conclusions: Our collective findings indicate that HMME-PDT therapy is effective and safe for PWS and support the utility of OCT in objective assessment of the efficacy of HMME-PDT.
ABSTRACT
Antimicrobial peptides (AMPs) have great potential for clinical treatment of bacterial infection due to the broad-spectrum and highly effective antibacterial activity. However, the easy degradation and inactivation in vivo has been a major obstacle for their application and an effective delivery system is demanding. The surface physicochemical properties of the carrier, including surface potential, surface polarity, pore structure and morphology, have exerted great effects on the adsorption and release behavior of AMPs. This study investigated the influence of micro/nano carriers with different hierarchical structures on the loading, release and biological behavior of AMPs. Three types of AMPs-loaded hydroxyapatite microspheres (HA/AMPs MSs) with different hierarchical structures (needle-like, rod-like, and flake-like) were developed, which was investigated by the surface morphology, chemical composition and surface potential in detail. The different hierarchical structures of hydroxyapatite microspheres (HA MSs) had noticeable impact on the loading and release behavior of AMPs, and the flake-like HA MSs with hierarchical structure showed the highest loading efficiency and long-lasting release over 9 days. Meanwhile, the stability of AMPs released from HA MSs was effectively maintained. Moreover, the antibacterial test indicated that the flake-like HA/AMPs MSs showed more sustained antibacterial properties among three composites. In view of the excellent biocompatibility and osteogenic property, high loading efficiency and the long-term release properties of HA MSs with hierarchical structure, the HA/AMPs MSs have a great potential in bone tissue engineering.
ABSTRACT
BACKGROUND: The effects of PSENEN mutations in patients with acne inversa (AI) are poorly understood. Hyperproliferation of follicular keratinocytes and resulting occlusion may constitute the initial pathophysiology. OBJECTIVE: To investigate the effects of PSENEN knockdown on γ-secretase subunits, biological behaviors, and related signaling pathways in keratinocytes. METHODS: HaCaT cells were divided into an experimental group (PSENEN knock down), a negative control group, and a blank control group. Whole transcriptome sequencing was used to measure differences in mRNA expression of the whole genome; real-time PCR and Western blotting were performed to determine the interference efficiency and the effects of interference on the components of γ-secretase and related molecules. CCK-8 was used to measure cell proliferation, and flow cytometry was used to measure apoptosis and the cell cycle. RESULTS: A comparison of five healthy controls with three patients with PSENEN mutation (c.66delG, c.279delC, c.229_230insCACC) revealed decreased expression of mRNA and protein in skin lesions of the experimental group. In this group, expression of the other components of γ-secretase presenilin C-terminal fragment decreased, expression of immature nicastrin increased, expression of mature nicastrin decreased, and expression of anterior pharynx defective-1 remained unchanged. KEGG analysis revealed that differentially expressed molecules were enriched in m-TOR signaling pathways. Subsequent verification confirmed that differences in PI3K-AKT-mTOR signaling pathway molecules, cell proliferation, apoptosis, cell cycle and the expression levels of Ki-67, KRT1, and IVL between the groups were not statistically significant. CONCLUSIONS: PSENEN mutations alone may be insufficient to cause the development of AI, or they may only induce a mild phenotype of AI.
Subject(s)
Amyloid Precursor Protein Secretases/genetics , Hidradenitis Suppurativa/genetics , Membrane Proteins/genetics , Amyloid Precursor Protein Secretases/metabolism , Case-Control Studies , Cell Line , Gene Knockdown Techniques , Hidradenitis Suppurativa/metabolism , Humans , Membrane Proteins/metabolism , Mutation , Signal Transduction , Exome SequencingSubject(s)
Carcinoma in Situ , Skin Abnormalities , Calcium-Transporting ATPases/genetics , Humans , MutationSubject(s)
Photochemotherapy , Telangiectasis , Hematoporphyrins , Humans , Telangiectasis/drug therapyABSTRACT
Nicastrin (NCSTN) mutations are associated with familial acne inversa (AI), and emerging evidence suggests that microRNAs (miRNAs) are involved in various skin diseases. However, whether NCSTN mutations affect miRNA levels and their subsequent signaling pathways in familial AI patients has not been studied. We aimed to elucidate the relationship between NCSTN mutations and familial AI pathogenesis by investigating differential miRNA expression and their related pathways. Combined with miRNA microarray data from familial AI patients, Ncstn keratinocyte-specific-knockout (NcstnΔKC) mice and bioinformatics predictions showed that NCSTN mutations led to decreased miR-30a-3p levels, which negatively regulated RAB31 expression. Moreover, enhanced RAB31 levels accelerated degradation of activated EGFR, leading to abnormal differentiation in keratinocytes. The impaired EGFR signaling and its effects on epidermal differentiation were also observed in familial AI patients and NcstnΔKC mice. Thus, our study showed that miR-30a-3p/RAB31/EGFR signaling pathway may play a key role in the pathogenesis of familial AI with NCSTN mutations.
Subject(s)
Amyloid Precursor Protein Secretases/genetics , Gene Expression Regulation , Hidradenitis Suppurativa/genetics , Membrane Glycoproteins/genetics , MicroRNAs/genetics , Mutation , rab GTP-Binding Proteins/genetics , Amyloid Precursor Protein Secretases/biosynthesis , Animals , Apoptosis/genetics , Cell Differentiation , DNA Mutational Analysis , ErbB Receptors/genetics , ErbB Receptors/metabolism , Hidradenitis Suppurativa/metabolism , Hidradenitis Suppurativa/pathology , Humans , Keratinocytes/metabolism , Keratinocytes/pathology , Membrane Glycoproteins/biosynthesis , Mice , Mice, Knockout , MicroRNAs/biosynthesis , Polymerase Chain Reaction , RNA/genetics , Signal Transduction , rab GTP-Binding Proteins/biosynthesisSubject(s)
Anal Canal/pathology , Asian People/genetics , Calcium-Transporting ATPases/genetics , Genitalia, Female/pathology , Mutation, Missense/genetics , Pemphigus, Benign Familial/genetics , Adult , Female , Humans , Pemphigus, Benign Familial/diagnosis , Skin Diseases/diagnosis , Skin Diseases/geneticsABSTRACT
Piebaldism is a rare autosomal dominant genodermatosis, manifesting as congenital and stable depigmentation of the skin and white forelock. It has been found to be associated with mutations in the KIT or SLUG genes. We report a Chinese piebaldism family including a 28-year-old woman and her 3-year-old son with characteristics of white patches and forelock associated with numerous brown macules and patches. Genomic DNA samples of the proband and her son were extracted from their peripheral blood. One hundred unrelated healthy individuals were used as controls. All coding regions of KIT, SLUG, and NF1 genes were amplified by polymerase chain reaction using exon flanking intronic primers and Sanger sequencings were performed. DNA sequencing revealed heterozygous missense c.2431T>G mutation in exon 17 of the KIT gene in the proband and the affected son. No potentially pathogenic variant was identified in SLUG or NF1 genes. The nucleotide substitution was not found in 100 unrelated control individuals. This study reveals a novel KIT mutation in piebaldism, and it further supports that café-au-lait macules and intertriginous freckling of piebaldism are parts of pigmented anomaly in piebaldism, which does not necessarily represent coexistence of neurofibromatosis type 1 (NF1).