Discrepancies in Perceived Indulgent Parenting, Relationship Satisfaction, and Psychological Well-Being of Adolescents and Parents.

Indulgent parenting has been associated with adolescents' psychological well-being problems; however, prior research has primarily relied on adolescents' report of such parenting behavior and its association with their own well-being, often overlooking parents' perceptions of indulgence and their own well-being. In this study, we address this gap in the literature by examining the agreement and disagreement between parents' and adolescents' perceptions of indulgent parenting and the implications for the psychological well-being of both adolescents and their parents. Further, we explore the role of adolescent-parent relationship satisfaction as a potential factor affecting these associations. Our investigation was based on data from 128 parent-adolescent dyads. Utilizing structural equation modeling with double-entry intraclass correlations (ICC_DE), our analyses revealed several main findings: (1) adolescents perceived higher levels of indulgent parenting than their parents did; (2) disagreement in perceived indulgent parenting between parents and adolescents was linked to psychological well-being problems for both adolescents and their parents; and (3) disagreement in perceptions in indulgent parenting had a stronger association with adolescents' well-being problems when adolescents reported greater relationship satisfaction with their parents. These findings provide insights into perceptions of indulgent parenting within parent-adolescent relationships and bring psychological implications for both adolescents and their parents.

An Open-Label, Uncontrolled, Single-Arm Clinical Trial of Tofacitinib, an Oral JAK1 and JAK3 Kinase Inhibitor, in Chinese Patients with Keloid.

BACKGROUND: The keloid treatment is still a thorny and complicated clinical problem, especially in multiple keloids induced by wound, severe burn, ethnic background or cultural behaviors, or unexplained skin healing. Mainstream treatments have limited efficacy in treating multiple keloids. As no oral treatment with painlessness and convenience is available, oral treatment strategies should be formulated. OBJECTIVES: This study aimed to investigate the efficacy and therapeutic mechanism of oral tofacitinib in keloid patients. METHODS: We recruited the 7 patients with keloid scars and prescribed 5 mg of tofacitinib twice a day orally with a maximum follow-up of 12 weeks. The Patient and Observer Scar Assessment Scale (POSAS), the Vancouver scar scale (VSS), ANTERA 3D camera, and the DUB Skin Scanner 75 were used to assess the characteristics of the lesion. Immunohistochemistry was performed to evaluate collagen synthesis, proliferation, and relative molecular pathways. Moreover, the effects of tofacitinib were assessed on keloid fibroblast in vitro. RESULTS: After 12 weeks of oral tofacitinib, significant improvement in POSAS, VSS, and Dermatology Life Quality Index (DLQI) scores was observed (p < 0.05). The volume, lesion height, and dermis thickness of the keloid decreased (p < 0.05). Moreover, significant decreases in the expression of collagen I, Ki67, p-STAT 3, and p-SMAD2 were observed after 12 weeks of administration. In vitro experiments suggested that tofacitinib treatment inhibits fibroblast proliferation and collagen I synthesis via suppression of STAT3 and SMAD2 pathway. CONCLUSION: Tofacitinib, a new candidate oral drug for keloid, could reduce keloid lesion volume by inhibiting collagen synthesis and inhibiting fibroblast proliferation, and alleviate itch and pain to obtain a better life quality.

Indulgent Parenting and the Psychological Well-Being of Adolescents and Their Parents.

Adolescence is a time for identity development and exploration. Indulgent parenting during adolescence could be developmentally inappropriate and could be associated with adolescent psychological well-being problems. Little research on indulgent parenting, however, has included and investigated both adolescent and parental well-being problems. To extend the literature, the current study used both adolescent and parental reports in a dyadic context to investigate the association between indulgent parenting and the psychological well-being problems of both adolescents and their parents. This study used a sample of 128 adolescent-parent dyads. The findings from the actor-partner interdependence model (APIM) suggested that (1) the adolescent perceptions of behavioral indulgent parenting were significantly related to their own well-being problems; (2) the parents' perceptions of relational and behavioral indulgent parenting were significantly related to their own well-being problems; and (3) no effects were found between adolescents and their parents. The findings from this study have implications for prevention and intervention programs to improve parenting practices and reduce parents' well-being problems.

The development of small molecules targeting methyltransferase-like 3.

In mammals, N6-methyladenosine (m6A) is thought to be the most common and conserved mRNA modification. Methyltransferase-like 3 (METTL3) is the primary regulator of m6A methyl-transformed modification. Small molecules targeting METTL3 could be effective therapeutics for many disorders, given that a large body of research has linked METTL3 dysregulation with a variety of diseases and altered physiological states, especially with the growth and initiation of cancer. Here, we systematically reviewed the discovery of small molecules targeting METTL3, as well as their future development, for researchers studying in the field.

Relief of Extracellular Matrix Deposition Repression by Downregulation of IRF1-Mediated TWEAK/Fn14 Signaling in Keloids.

Keloids represent a fibrotic disorder characterized by the excessive deposition of extracellular matrix (ECM). However, the mechanisms through which ECM deposition in keloids is regulated remain elusive. In this study, we found that the expression of both TWEAK and its cognate receptor Fn14 was significantly downregulated in keloids and that TWEAK/Fn14 signaling repressed the expression of ECM-related genes in keloid fibroblasts. The IRF1 gene was essential for this repression, and the TWEAK/Fn14 downstream transcription factor p65 directly bound to the promoter of the IRF1 gene and induced its expression. Furthermore, in patients with keloid, the expression of TWEAK and Fn14 was negatively correlated with that of ECM genes and positively correlated with that of IRF1. These observations indicate that relief of TWEAK/Fn14/IRF1-mediated ECM deposition repression contributes to keloid pathogenesis, and the identified mechanism and related molecules provide potential targets for keloid treatment in the future.

TSP1 promotes fibroblast proliferation and extracellular matrix deposition via the IL6/JAK2/STAT3 signalling pathway in keloids.

Keloids are benign fibroproliferative diseases with abnormally proliferated bulges beyond the edge of the skin lesions, and they are characterized by uncontrolled fibroblast proliferation and excessive extracellular matrix deposition in the dermis. However, the definite mechanisms that increase fibroblast proliferation and collagen deposition in keloids remain unclear. Thrombospondin 1 (TSP1) has been suggested to play an important role in wound healing and fibrotic disorders, but its role in keloids is unknown. In this study, we aimed to clarify the specific role of TSP1 in keloids and explore the potential mechanism. Our results demonstrated that TSP1 was highly expressed in keloid lesions compared to normal skin. Knockdown of TSP1 in keloid fibroblasts decreased cell proliferation and collagen I deposition. Exogenous TSP1 treatment increased cell proliferation and collagen I deposition in normal fibroblasts. We further investigated the underlying mechanism and found that TSP1 promoted fibroblast proliferation and extracellular matrix deposition by upregulating the IL6/JAK2/STAT3 pathway. Moreover, we verified that TSP1 expression was positively correlated with IL6/STAT3 signalling activity in keloids. Taken together, our findings indicate that TSP1 promotes keloid development via the IL6/JAK2/STAT3 signalling pathway and blocking TSP1 may represent a potential strategy for keloid therapy.

Pyroptosis executor gasdermin D plays a key role in scleroderma and bleomycin-induced skin fibrosis.

The NLRP3 inflammasome and IL-1ß are essential for scleroderma pathogenesis. Nevertheless, the role of pyroptosis executor gasdermin D(GSDMD), which is a downstream molecule of NLRP3 and is required for IL-1ß release in some situations, has not yet been well elucidated in scleroderma. Here, we found that GSDMD was significantly up-regulated and activated in the skin of scleroderma patients and bleomycin-induced mouse model. What's more, the ablation of GSDMD ameliorates bleomycin-induced skin fibrosis according to HE staining, Masson staining and the detection of hydroxyproline contents. GSDMD deficiency also impaired macrophages infiltration and reduced inflammation response. Furthermore, the loss of GSDMD reduced Th17 differentiation in vivo and in vitro. Collectively, these findings provide the first demonstration that GSDMD related pyroptosis plays an important role in scleroderma pathogenesis.

Single-cell RNA-seq reveals fibroblast heterogeneity and increased mesenchymal fibroblasts in human fibrotic skin diseases.

Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix. Fibroblasts are found to be heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. In this study, we explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases, by using single-cell RNA-seq. Our results indicate that keloid fibroblasts can be divided into 4 subpopulations: secretory-papillary, secretory-reticular, mesenchymal and pro-inflammatory. Interestingly, the percentage of mesenchymal fibroblast subpopulation is significantly increased in keloid compared to normal scar. Functional studies indicate that mesenchymal fibroblasts are crucial for collagen overexpression in keloid. Increased mesenchymal fibroblast subpopulation is also found in another fibrotic skin disease, scleroderma, suggesting this is a broad mechanism for skin fibrosis. These findings will help us better understand skin fibrotic pathogenesis, and provide potential targets for fibrotic disease therapies.