The Innovative and Evolving Landscape of Topical Exosome and Peptide Therapies: A Systematic Review of the Available Literature.

Topical antiaging therapies provide noninvasive delivery of active therapeutics. Exosomes, or extracellular nanovesicles, and peptides, small strings of amino acids, have shown promise as topical therapies in early trials, but neither is FDA approved. This review aims to elucidate the current and future landscape of topical exosomes and peptides as therapeutics for skin rejuvenation. A literature search was conducted using the keywords "peptides" OR "exosomes" AND "skin" OR "rejuvenation." Primary endpoints included mechanisms of action in humans or live animals as well as clinical data supporting the use of exosomes or peptides topically for skin rejuvenation or wound healing. Secondary endpoints were safety, side effects, and efficacy. The articles were collected, organized, and sorted using the Covidence software (Melbourne, Australia) for systematic review. Nine articles evaluating topical application of exosomes and 9 of peptides met inclusion criteria. Topical exosomes were found to increase collagen deposition, accelerate wound healing, and improve overall cosmesis. Several clinical trials are currently underway. Topical peptides were found to improve appearance of fine lines and wrinkles, elasticity and viscoelasticity, skin texture, skin thickness, and the potential for accelerated wound healing. Peptides are quite common in "cosmeceutical" products, and several patents have been filed for topical peptide products aimed at increasing skin rejuvenation. This could indicate a movement toward pursuing FDA approval. The future of topical exosome and peptide products for the purpose of skin rejuvenation appears promising. Preliminary data from the studies reviewed here indicates that these products have the potential to be safe and effective.

Defining the Ideal Reduction Mammoplasty: A Crowdsourcing Study.

BACKGROUND: Reduction mammoplasty relieves macromastia symptoms while improving breast aesthetics, though the ideal breast aesthetically has been shown to differ culturally in previous crowdsourcing studies. Better understanding these differences can aid in setting postoperative expectations. OBJECTIVES: The aim of this study was to characterize the ideal reduction mammoplasty according to demographics such as gender, ethnicity, socioeconomic status, and education. METHODS: A crowdsourcing platform was used to collect 10,169 de-identified responses. Users completed one of three surveys, either a preoperative, postoperative, or preoperative and postoperative paired survey. The preoperative and postoperative surveys addressed 10 breast measurements including upper breast slope, projection proportion, nipple position, breast width, and breast fullness. The paired pre- and postoperative survey assessed nipple areolar complex (NAC), chest fit, symmetry improvement, and scarring. RESULTS: Preoperative images were rated more aesthetic than postoperative images. This was consistent across all demographics evaluated. Female, African American, Asian, participants aged 55+, and participants with no high school degree or a graduate degree found the most improvement in breast symmetry (p = 0.001, p = 0.002, p = 0.027, p < 0.001, p = 0.01). Male and Hispanic participants were most likely to see no change in symmetry (p = 0.008, p = 0.04), and South Asian participants found breasts less symmetric postoperative (p < 0.001). There were significant demographic differences in aesthetic ratings of NAC, scarring, and breast fit. CONCLUSIONS: Perceived breast aesthetics after reduction mammoplasty vary significantly across demographics including gender, ethnicity, age, socioeconomic status, and educational achievement. Surgeons should consider demographics when planning each patient's reduction mammoplasty.

Staufen1 Represses the FOXA1-Regulated Transcriptome by Destabilizing FOXA1 mRNA in Colorectal Cancer Cells.

Transcription factors play key roles in development and disease by controlling gene expression. Forkhead box A1 (FOXA1), is a pioneer transcription factor essential for mouse development and functions as an oncogene in prostate and breast cancer. In colorectal cancer (CRC), FOXA1 is significantly downregulated and high FOXA1 expression is associated with better prognosis, suggesting potential tumor suppressive functions. We therefore investigated the regulation of FOXA1 expression in CRC, focusing on well-differentiated CRC cells, where FOXA1 is robustly expressed. Genome-wide RNA stability assays identified FOXA1 as an unstable mRNA in CRC cells. We validated FOXA1 mRNA instability in multiple CRC cell lines and in patient-derived CRC organoids, and found that the FOXA1 3'UTR confers instability to the FOXA1 transcript. RNA pulldowns and mass spectrometry identified Staufen1 (STAU1) as a potential regulator of FOXA1 mRNA. Indeed, STAU1 knockdown resulted in increased FOXA1 mRNA and protein expression due to increased FOXA1 mRNA stability. Consistent with these data, RNA-seq following STAU1 knockdown in CRC cells revealed that FOXA1 targets were upregulated upon STAU1 knockdown. Collectively, this study uncovers a molecular mechanism by which FOXA1 is regulated in CRC cells and provides insights into our understanding of the complex mechanisms of gene regulation in cancer.

Hypothyroxinemia and weight velocity in preterm infants.

OBJECTIVES: Hypothyroxinemia of prematurity (HOP) is characterized by low free thyroxine (FT4) associated with low or normal thyroid stimulating hormone (TSH). The objective of this study is to define FT4 and TSH values in very preterm infants (<32 weeks postmenstrual age, PMA) and correlate hypothyroxinemia and levothyroxine treatment with growth velocity at 28 days and 36 weeks PMA. METHODS: Preterm neonates <32 weeks PMA admitted to the regional neonatal intensive care unit (NICU) at the Children's Hospital of Georgia (USA) between January 2010 and July 2022 were routinely screened for hypothyroxinemia. FT4 and TSH values were obtained on 589 eligible neonates between day of life (DOL) 4 and 14. Growth velocity (g/kg/day) from DOL 14 to DOL 28 and 36-weeks PMA were calculated for each neonate and potential explanatory variables (PMA, sex, and race) were incorporated into multivariate regression models to identify associations between HOP and growth velocity. RESULTS: In 589 preterm infants, PMA at birth was strongly associated inversely with FT4 (R=0.5845) and modestly with TSH (R=0.2740). Both FT4 and gestational age, but not TSH or levothyroxine treatment, were associated with growth velocity at 28 days of life and at 36 weeks PMA. CONCLUSIONS: We provide a large data set for identifying FT4 and TSH measurements and identify hypothyroxinemia of prematurity as a potential mediator of slow postnatal growth in very preterm infants.

Enhanced recovery after surgery pathways for deep inferior epigastric perforator flap breast reconstruction: A systematic review and meta-analysis.

BACKGROUND: Deep inferior epigastric perforator (DIEP) surgery is one of the most difficult breast reconstruction techniques available, both in terms of operating complexity and patient recovery. Enhanced recovery after surgery (ERAS) pathways were recently introduced in numerous subspecialties to reduce recovery time, patient pain, and cost by providing multimodal perioperative care. Plastic surgery has yet to widely integrate ERAS with DIEP reconstruction, mostly due to insufficient data on patient outcomes with this combined approach. METHODS: Five major medical databases were queried using predetermined search criteria according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Statistical analysis was performed using Cochrane's RevMan (v5.4). RESULTS: A total of 466 articles were identified. A total of 14 studies were included in the review with a combined sample of 2102 patients. Eight studies were included in the meta-analysis with a combined sample of 1679 patients. On average, the included studies utilized 11.69 of 18 suggested protocols for ERAS with breast reconstruction. Our primary outcome, length of stay, was reduced by a mean of 1.12 (95% confidence interval [CI] [-1.30, -0.94], n = 1627, p < 0.001) days in the ERAS group. Postoperative oral morphine equivalents (OME) were also reduced in the ERAS group by 104.02 (95% CI [-181.43, -26.61], n = 545, p = 0.008) OME. The ERAS group saw a significant 3.54 (95% CI [-4.43, -2.65], n = 527, p < 0.001) standardized mean difference cost reduction relative to the control groups. The surgery time was reduced by 60.46 (95% CI [-125, 4.29], n = 624, p < 0.07) min, although this was not statistically significant. CONCLUSIONS: The ERAS pathway in DIEP breast reconstruction is consistently associated with reduced hospital stay, opioid use, and patient cost. Moreover, there appears to be no evidence of serious adverse outcomes associated with the application of the ERAS protocol.

An Evolutionarily Conserved AU-Rich Element in the 3' Untranslated Region of a Transcript Misannotated as a Long Noncoding RNA Regulates RNA Stability.

One of the primary mechanisms of post-transcriptional gene regulation is the modulation of RNA stability. We recently discovered that LINC00675, a transcript annotated as a long noncoding RNA (lncRNA), is transcriptionally regulated by FOXA1 and encodes a highly conserved small protein that localizes to the endoplasmic reticulum, hence renamed as FORCP (FOXA1-regulated conserved small protein). Here, we show that the endogenous FORCP transcript is rapidly degraded and rendered unstable as a result of 3'UTR-mediated degradation. Surprisingly, although the FORCP transcript is a canonical nonsense-mediated decay (NMD) and microRNA (miRNA) target, we found that it is not degraded by NMD or miRNAs. Targeted deletion of an evolutionarily conserved region in the FORCP 3'UTR using CRISPR/Cas9 significantly increased the stability of the FORCP transcript. Interestingly, this region requires the presence of an immediate downstream 55-nt-long sequence for transcript stability regulation. Functionally, colorectal cancer cells lacking this conserved region expressed from the endogenous FORCP locus displayed decreased proliferation and clonogenicity. These data demonstrate that the FORCP transcript is destabilized via conserved elements within its 3'UTR and emphasize the need to interrogate the function of a given 3'UTR in its native context.

Interrogating lncRNA functions via CRISPR/Cas systems.

Long noncoding RNAs (lncRNAs) are an increasing focus of investigation due to their implications in diverse biological processes and disease. Nevertheless, the majority of lncRNAs are low in abundance and poorly conserved, posing challenges to functional studies. The CRISPR/Cas system, an innovative technology that has emerged over the last decade, can be utilized to further understand lncRNA function. The system targets specific DNA and/or RNA sequences via a guide RNA (gRNA) and Cas nuclease complex. We and others have utilized this technology in various applications such as lncRNA knockout, knockdown, overexpression, and imaging. In this review, we summarize how the CRISPR/Cas technology provides new tools to investigate the roles and therapeutic implications of lncRNAs.