The Inhibition of Adipose-Derived Stem Cells on the Invasion of Keloid Fibroblasts.

Background: Keloids represent the dysregulation of cutaneous wound healing caused by aberrant fibroblast activities. Adipose-derived stem cells have been recognized as a promising treatment for keloids. However, the molecular mechanisms have not been fully elucidated. Objectives: to explicitly demonstrate the relationship between adipose-derived stem cells alleviating keloids and alterations of Col-1, Col-3, CTGF, and P-4-HB. Methods: Skin biopsies were obtained from 10 keloid patients and 9 healthy volunteers. Fibroblasts isolated from all samples were divided into two groups, one co-cultured with adipose-derived stem cells and the other grown independently. We compared the wound-healing rates, fibroblast survival rates, apoptosis rates, mRNA expressions, and protein levels of Col-1, Col-3, CTGF, and P-4-HB between separated groups. Results: We found no significant differences between normal fibroblasts and keloid fibroblasts in terms of wound-healing rate, survival rate, or apoptosis rate at the baseline. With adipose-derived stem cells, wound-healing rate and survival rate of normal fibroblasts were promoted, whereas in keloid fibroblasts, they were reduced. The apoptosis rate of normal fibroblasts and keloid fibroblasts were restrained, with the restraint in keloid fibroblasts being more evident. The protein levels of Col-3, CTGF, and P-4-HB were lower in keloid fibroblasts co-cultured with adipose-derived stem cells than in normal fibroblasts under similar conditions. Conclusions: Adipose-derived stem cells strongly suppressed keloid fibroblasts' proliferative and invasive behavior. However, adipose-derived stem cells negatively regulated keloid fibroblast apoptosis. Adipose-derived stem cells can be a potential keloid therapy worth further investigation.

[Early motor development in children with Williams syndrome]. / Williams综合征儿童早期运动发育特征.

OBJECTIVES: To study the early motor development of children with William syndrome (WS). METHODS: The medical data of 59 children with WS (40 males and 19 females) aged 0-24 months from September 2018 to August 2021 were retrospectively analyzed. Based on the test results of the Peabody Developmental Motor Scale II, the motor development ability of the children of different ages was analyzed. RESULTS: There was no significant difference in age and motor quotient between boys and girls (P>0.05). For the age groups of <6 months, 6 to <12 months, 12 to <18 months, and 18 to 24 months, the gross-motor quotients were 94±5, 78±11, 71±8, and 63±8, respectively, and the fine-motor quotients were 94±5, 80±10, 74±9, and 65±9, respectively. Both the gross- and fine-motor quotients significantly decreased with age (P<0.05). For the above age groups, the rates of gross-motor abnormalities were 0%, 53%, 87%, and 93%, respectively, and the rates of fine-motor development abnormalities were 0%, 47%, 67%, and 93%, respectively. The rates of gross- and fine-motor development abnormalities increased significantly with age (P<0.05). CONCLUSIONS: Children with WS have no obvious motor delays within 6 months of age, but present with decreasing motor ability and an increasing incidence of motor delays with age. Therefore, it is necessary to follow up their motor abilities and provide early intervention to decrease the incidence of motor developmental delays.

Clinical phenotypes study of 231 children with Williams syndrome in China: A single-center retrospective study.

BACKGROUND: Williams syndrome (WS) is a multisystem neurodevelopmental disorder caused by microdeletions in 7q11.23. This study aims to characterize the clinical phenotypes of Chinese children with WS to help for the early diagnosis and intervention of this disease. METHODS: 231 children diagnosed with WS were retrospectively recruited to the study. Clinical data were analyzed to obtain the incidence of different clinical phenotypes. The occurrence of phenotypes and the influence of gender and age on the incidence of different phenotypes were analyzed. RESULTS: All WS exhibited facial dysmorphism (100.0%). The majority had neurodevelopmental disorder (91.8%), hoarseness (87.4%) and cardiovascular anomalies (85.7%). The incidence of short stature (46.9%), inguinal hernia (47.2%), hypercalciuria (29.10%), hypercalcemia (9.1%), subclinical hypothyroidism (26.4%) and hypothyroidism (7.4%) were relatively higher. Gender differences were found in supravalvular aortic stenosis (SVAS, p < .001), ventricular septal defect (VSD, p < .05), inguinal hernia (p < .001), superior pulmonary stenosis (SVPS, p < .05) and neurodevelopmental disorder (p < .05). The incidence of neurodevelopmental disorder in WS increased with age (p < .05) while cardiovascular anomalies (p < .001), short stature (p < .001), hypercalciuria (p < .001) and hypercalcemia (p < .01) decreased with age. CONCLUSIONS: Facial dysmorphism, neurodevelopmental disorder, hoarseness and cardiovascular anomalies were the most common phenotypes. Genetic testing should be suggested to confirm the diagnosis for children with the above abnormalities. Gender and age should be taken into account when making diagnosis and intervention.

Differential Regulation of Integrin α5 and ß4 in Normal and Psoriatic Epidermal Keratinocytes

Abstract Psoriasis is a chronic skin inflammation, characterized by impaired differentiation, hyperproliferation of keratinocytes involving pro-inflammatory factors interleukin (IL)-13/17A, tumor necrosis factor (TNF)-α, interferon (IFN)-γ. Among the integrin family, α5 is important for blood vessel formation, and ß4 for proliferation, differentiation of keratinocytes. To investigate the expression and regulation of integrin α5 and ß4 in psoriatic keratinocytes. Skin biopsies were obtained from 14 psoriatic patients and 12 normal volunteers. We compared the immunolocalization and regulation of α5 and ß4 between the psoriatic and normal ones, before and after incubation with MEK/ERK pathway inhibitor U0126 by immunohistochemistry and western blot separately. Immunohistochemistry showed psoriatic keratinocytes had higher α5 than normal ones. According to western blot, IL-17A and IL-13 increased normal keratinocytes' α5 and ß4 respectively, but psoriatic keratinocytes were the exact opposite. Incubated with U0126, normal keratinocytes' α5 was enhanced by the 5 cytokines ; while IL-13/17A, IFN-γ suppressed ß4. Psoriatic keratinocytes' α5 was increased by IL-13/17A, decreased by IFN-γ; but ß4 increased by IL-17A, IFN-γ. IL-13/17A, TNF-α, IFN-γ regulate α5 and ß4 through ERK pathway whether normal or psoriasis. The normal and psoriatic keratinocytes respond to the same cytokines differently

Indirect Regulation and Equilibrium of p35 and p40 Subunits of Interleukin (IL)-12/23 by Ustekinumab in Psoriasis Treatment.

BACKGROUND Ustekinumab, a human-derived monoclonal antibody that targets the p40 subunit of interleukin (IL)-12 and IL-23, has excellent clinical efficacy and safety in treating psoriasis, with a long half-life. However, no reports have described the use of human skin/serum samples to elucidate its molecular mechanisms. MATERIAL AND METHODS Twenty-four psoriasis patients were enrolled in our double-blind study and randomly divided into placebo and ustekinumab-administered groups. Dynamic changes in psoriasis area-severity index scores, and mRNA and protein levels of p35 and p40 were analyzed at 3 time points (before treatment and during the 12th and 24th weeks of treatment). RESULTS Ustekinumab initially increased and then decreased p35 mRNA expression, but increased p40 mRNA levels throughout the study. The p35 protein levels were not significantly altered, while p40 protein levels were increased after the first 2 injections but decreased after the third injection. CONCLUSIONS We concluded that 2 equilibria influence the efficacy of ustekinumab against psoriasis. First, because of the dual roles of p35 in psoriasis pathogenesis, homeostasis occurs between p35 and p40 expression levels. The second balance lies between the upregulation of p40 mRNA levels and the ability of ustekinumab to neutralize the function of the elevated p40 protein.

Ustekinumab treats psoriasis by suppressing RORC and T-box but its suppression of GATA restrains its efficacy

Psoriasis is a T-cell mediated disease that involves IL-23/Th17 and IL-12/Th1 axes. Ustekinumab, a fully human monoclonal antibody targeting the p40 subunit of both IL-12 and IL-23, has proven to be efficient and safe for treating patients with psoriasis. Yet, there have been no reports with human skin/blood samples that would elucidate the molecular mechanisms by which ustekinumab calms psoriasis skin lesions. To investigate the efficacy and molecular pathway (RORC, t-BOX and GATA) of ustekinumab in treating patients with psoriasis skin lesions. A total of 30 patients with psoriasis were randomized into placebo group and treatment group. PASI of each patient was calculated at 0, 12 and 24 weeks post-treatment. The mRNA levels of RORC, t-BOX and GATA in peripheral blood mononuclear cells separated from patients' whole blood were analyzed using qPCR. Decreased mRNA of RORC, t-BOX and GATA were observed after continuous injections, indicating that ustekinumab exerts its effect by interacting with these molecules; while no significant difference in foxp3 mRNA levels were found between placebo group and treatment group.