Sex-specific differences in oxidative stress markers and collagen expression in perioral skin wrinkling.

Wrinkling is the hallmark of skin ageing. We previously reported that perioral wrinkling is more severe in females; however, the molecular basis is unknown. This study assessed sex differences in the molecular expression of key ageing regulators in perioral skin. Twelve subjects (n = 6 male/female) were enrolled in this cross-sectional study and biopsies were taken from the perioral and periocular regions. RNA expression of collagen I, collagen III, cysteine-rich angiogenic inducer 61 (CYR61) and insulin-like growth factor 1 (IGF-1) was assessed by qPCR. There was no difference between females' and males' Griffith's grades (6 and 5.67, respectively, p = 0.092) or periocular wrinkling grades (3.2 and 2.6, p = 0.421), but females had more severe perioral wrinkling grades than males (6.2 and 2.8, p = 0.020). Females not only expressed significantly more CYR61 (p = 0.018) in the perioral region than malesm but also expressed more collagen III (p = 0.016). There was no difference in collagen I (p = 0.115) or IGF-1 (p = 0.124) expression in the perioral region between sexes. In the periocular region, there were no significant differences between sexes in the expression of all four markers. The significant molecular differences in the perioral region between the sexes may contribute to the greater perioral skin wrinkling seen clinically in females.

Platelet-Rich Plasma and Its Utilities in Alopecia: A Systematic Review.

BACKGROUND: The use of platelet-rich plasma is becoming more prevalent in the field of dermatology. Variable preparation techniques and treatment methods have been described with reported success in alopecia. OBJECTIVE: To consolidate the available evidence of platelet-rich plasma and its utility in the treatment of alopecia for the practicing dermatologist. METHODS: Evaluating the available evidence up to May 31, 2018, a search was conducted in the PubMed database for "platelet rich plasma" or "platelet releasate" or "platelet gel" or "PRP" and "dermatology" or "skin" or "hair" or "cutaneous." RESULTS: Nineteen articles met the inclusion criteria for analysis including 3 alopecia areata studies with a total of 71 patients and 16 androgenetic alopecia studies with a total of 389 patients. Although the heterogeneity of the studies prevented direct comparisons and subsequent statistical analysis, the majority demonstrated that platelet-rich plasma produced successful hair growth in androgenetic alopecia and alopecia areata. CONCLUSION: This review advocates for the use of platelet-rich plasma in 3 to 4 monthly sessions for the treatment of alopecia. Future studies should include a detailed description of the platelet-rich plasma isolation process to allow for comparison among studies, provide reproducibility, and generate a standardized treatment protocol.

Platelet-rich plasma and its utility in medical dermatology: A systematic review.

The field of dermatology has seen numerous therapeutic innovations in the past decade with platelet-rich plasma (PRP), recently garnering significant interest in alopecia, acne scarring, and skin rejuvenation. In other conditions of dermatology, such as chronic wounds and vitiligo, PRP has been investigated but has received less attention. The objective of this literature review was to focus on conditions of medical dermatology and to consolidate the available evidence on PRP for the practicing dermatologist. This review evaluates the literature up to October 31, 2018, and a search was conducted in the PubMed database for "platelet-rich plasma," "platelet releasate," "platelet gel," "platelet-rich fibrin" or "PRP" and "dermatology," "skin," "cutaneous," "wound," or "ulcer." In total, 14 articles met the inclusion criteria for this review. In studies representing Levels of Evidence 1b-4 according to the Centre for Evidence-Based Medicine, Oxford, PRP significantly improved wound healing in chronic diabetic ulcers, venous ulcers, pressure ulcers, leprosy ulcers, acute traumatic wounds, and ulcers of multifactorial etiologies. Two studies also documented benefits of adjunctive PRP in stable vitiligo. In chronic wounds of multiple etiologies and vitiligo, PRP warrants further investigation because it represents a potential therapeutic adjunct or alternative with a favorable side effect profile.

Platelet-rich plasma and its utility in the treatment of acne scars: A systematic review.

The field of dermatology has seen numerous therapeutic innovations in the past decade, with platelet-rich plasma recently garnering significant interest in acne scarring. This review consolidates the available evidence on platelet-rich plasma for the practicing dermatologist and evaluates the current evidence up to May 31, 2018. A search was conducted in the PubMed database for the terms platelet-rich plasma or platelet releasate or platelet gel or PRP and dermatology or skin or acne or scar or cutaneous, with 13 articles meeting the inclusion criteria. The quality of each individual study was evaluated, and levels of evidence were assigned according to the Centre for Evidence-Based Medicine, Oxford, United Kingdom. This review reveals that activated, leukocyte- and platelet-rich plasma in combination with fractional ablative laser treatment administered in 2 or 3 sequential sessions 1 month apart improves the appearance of acne scars. The evidence for the use of platelet-rich plasma with microneedling is less supportive. Because of the heterogeneity of the studies and widely variable outcome measures, comparison between platelet-rich plasma treatments and subsequent statistical analysis could not be performed. Although these studies use various subjective and objective evaluation methods, the addition of platelet-rich plasma provides improvements in acne scarring, higher patient satisfaction, and decreased postprocedure downtime.

Bmi1 is required for the initiation of pancreatic cancer through an Ink4a-independent mechanism.

Epigenetic dysregulation is involved in the initiation and progression of many epithelial cancers. BMI1, a component of the polycomb protein family, plays a key role in these processes by controlling the histone ubiquitination and long-term repression of multiple genomic loci. BMI1 has previously been implicated in pancreatic homeostasis and the function of pancreatic cancer stem cells. However, no work has yet addressed its role in the early stages of pancreatic cancer development. Here, we show that BMI1 is required for the initiation of murine pancreatic neoplasia using a novel conditional knockout of Bmi1 in combination with a Kras(G12D)-driven pancreatic cancer mouse model. We also demonstrate that the requirement for Bmi1 in pancreatic carcinogenesis is independent of the Ink4a/Arf locus and at least partially mediated by dysregulation of reactive oxygen species. Our data provide new evidence of the importance of this epigenetic regulator in the genesis of pancreatic cancer.

p16INK4A and p14ARF tumor suppressor pathways are deregulated in malignant rhabdoid tumors.

Malignant rhabdoid tumors (MRTs) are aggressive tumors associated with mutations in the SMARCB1 gene. In experimental systems, the loss of SMARCB1 is hypothesized to alter p16(INK4A) pathways resulting in the repression of tumor suppressors. To determine whether these pathways are deregulated in human MRT, we used immunohistochemistry on tissue microarrays to evaluate p16(INK4A)/E2F1/RB and p14(ARF)/MDM2/p53 pathways in 25 atypical teratoid/rhabdoid tumors (AT/RT) and 11 non-CNS MRT. p16(INK4A) was negative or showed focal weak expression. p16(INK4A) downstream targets CDK4/cyclin D1/ppRB were variably expressed at moderate to low levels; E2F1 was negative. Unexpectedly, p14(ARF) expression was seen in many cases, which correlated positively with p53 and inversely with MDM2 immunostaining in AT/RT. TP53 mutational analysis in 19 of 25 AT/RT and in 8 of 11 non-CNS MRT cases showed point mutations in only 3 AT/RT cases, suggesting that p53 expression was driven mainly by p14(ARF). Finally, nucleophosmin, a protein that stabilizes p53, was positive in most cases and colocalized with p53. Together, these data suggest that, in MRT, there is deregulation not only of p16(INK4A) but also of the p14(ARF) pathway. These results provide insights into cell cycle deregulation in the pathogenesis of human MRT and may aid in the design and evaluation of potential therapies for these tumors.

E2F1 localizes predominantly to neuronal cytoplasm and fails to induce expression of its transcriptional targets in human immunodeficiency virus-induced neuronal damage.

As human immunodeficiency virus (HIV) does not induce neuronal damage by direct infection, the mechanisms of neuronal damage or loss in HIV-associated dementia (HAD) remain unclear. We have shown previously that immunoreactivity of transcription factor, E2F1, increases in neurons, localizing predominantly to the cytoplasm, in HIV-associated pathologies. Here we confirm that E2F1 localization is predominantly cytoplasmic in primary postmitotic neurons in vitro and cortical neurons in vivo. To determine whether E2F1 contributes to neuronal death in HAD via transactivation of target promoters, we assessed the mRNA and protein levels of several classical E2F1 transcriptional targets implicated in cell cycle progression and apoptosis in an in vitro model of HIV-induced neurotoxicity and in cortical autopsy tissue from patients infected with HIV. By Q-PCR, we show that mRNA levels of E2F1 transcriptional targets implicated in cell cycle progression (E2F1, Cyclin A, proliferating cell nuclear antigen (PCNA), and dyhydrofolate reductase (DHFR)) and apoptosis (caspases 3, 8, 9 and p19(ARF)) remain unchanged in an in vitro model of HIV-induced neurotoxicity. Further, we show that protein levels of p19(ARF), Cyclin A, and PCNA are not altered in vitro or in the cortex of patients with HAD. We propose that the predominantly cytoplasmic localization of E2F1 in neurons may account for the lack of E2F1 target transactivation in neurons responding to HIV-induced neurotoxicity.