Retinol semisolid preparations in cosmetics: transcutaneous permeation mechanism and behaviour.

Retinol is widely used to treat skin ageing because of its effect on cell differentiation, proliferation and apoptosis. However, its potential benefits appear to be limited by its skin permeability. Herein, we investigated the transcutaneous behavior of retinol in semisolid cosmetics, in both in vitro and in vivo experiments. In vitro experiments used the modified Franz diffusion cell combined with Raman spectroscopy. In in vivo experiments, the content of retinol in rat skin and plasma was detected with HPLC. Retinol in semisolid cosmetics was mainly concentrated in the stratum corneum in the skin of the three animal models tested, and in any case did not cross the skin barrier after a 24 h dermatologic topical treatment in Franz diffusion cells tests. Similar results were obtained in live mice and rats, where retinol did not cross the skin barrier and did not enter the blood circulation. Raman spectroscopy was used to test the penetration depth of retinol in skin, which reached 16 µm out of 34 µm in pig skin, whereas the skin of mouse and rat showed too strong bakground interference. To explore epidermal transport mechanism and intradermal residence, skin transcriptomics was performed in rats, which identified 126 genes upregulated related to retinol transport and metabolism, relevant to the search terms "retinoid metabolic process" and "transporter activity". The identity of these upregulated genes suggests that the mechanism of retinol action is linked to epidermis, skin, tissue and epithelium development.

Polypyrimidine Tract-Binding Protein Enhances Zika Virus Translation by Binding to the 5' UTR of Internal Ribosomal Entry Site.

Objectives To identify the 5' untranslated region of Zika virus (ZIKV5'UTR) RNA-binding proteins and to investigate the impact of the binding protein on the activity of internal ribosomal entry site (IRES) located in ZIKV5'UTR and virus production. Methods Interacting proteins in U251 cells were captured using tRSA-tagged ZIKV 5'UTR RNA and tRSA-ZIKV 5'UTR RNA-binding proteins were visualized by SDS-PAGE silver staining. Subsequently, liquid chromatography-tandem mass spectrometry (LC-MS/MS), bioinformatics analysis, and western blot were used to identify the candidate proteins binding to ZIKV5'UTR. Dicistronic expression assay and plaque forming assay were performed to analyze the effect of the binding protein on ZIKV IRES activity and ZIKV production. Results tRSA RNA pull-down assay, LC-MS/MS, and western blot analysis showed that polypyrimidine tract-binding protein (PTB) bound to the ZIKV 5'UTR Furthermore, dual luciferase reporter assay revealed that overexpression of PTB significantly enhanced the IRES activity of ZIKV (t = 10.220, P < 0.001), while PTB knockdown had the opposite effect (t = 4.897, P < 0.01). Additionally, virus plaque forming assay demonstrated that up-regulation of PTB expression significantly enhanced viral titer (t = 6.400, P < 0.01), whereas reducing PTB expression level weakened virus infectivity (t = 5.055, P < 0.01). Conclusion PTB positively interacts with the ZIKV 5'UTR and enhances IRES activity and virus production.

The effect of multiple single cannulation technique on complications of arteriovenous fistulae: A meta-analysis.

OBJECTIVE: To evaluate the effect of multiple single cannulation technique on the complications of arteriovenous fistula. METHODS: A comprehensive literature search was conducted to investigate the impact of multiple single cannulation technique on the complications of arteriovenous fistula. The search was performed in both Chinese and English databases including Wanfang Medicine, China National Knowledge Infrastructure, Vip, Pubmed, Embase, and The Cochrane Library, with a search period up to December 20, 2023. Following literature screening and data extraction, the quality of the included studies was assessed using the Cochrane Bias Assessment Tool for Randomized Controlled Trials. Statistical analysis was performed using Review Manager version 5.3. RESULTS: Thirteen papers, totaling 1299 patients, were included in the analysis. The experimental group consisted of 646 patients, while the control group had 595 patients. The meta-analysis revealed that the multiple single cannulation technique was more effective than rope ladder cannulation and buttonhole cannulation in reducing the incidence of angiomas (odds ratio [OR] = 0.19; 95% confidence interval [CI] = 0.10-0.35), stenosis (OR = 0.22; 95% CI 0.13-0.39), thrombosis (OR = 0.17; 95% CI = 0.07-0.39), and blood seepage (OR = 0.13; 95% CI = 0.08-0.21) of arteriovenous fistulas (P < .05). Additionally, it was found to increase the success rate of nurses' single cannulation (OR = 4.20; 95% CI = 1.78-9.95) of arteriovenous fistulas (P < .05). CONCLUSION: Multiple single cannulation technique could effectively reduce the incidence of complications of arteriovenous fistula, improve the success rate of cannulation, prolong the life span of arteriovenous fistula, and prolong the survival cycle of hemodialysis patients.

Development of an agroinfiltration-based transient hairpin RNA expression system in pak choi leaves (Brassica rapa ssp. chinensis) for RNA interference against Liriomyza sativae.

The vegetable leafminer (Liriomyza sativae) is a devastating invasive pest of many vegetable crops and horticultural plants worldwide, causing serious economic loss. Conventional control strategy against this pest mainly relies on the synthetic chemical pesticides, but widespread use of insecticides easily causes insecticide resistance development and is harmful to beneficial organisms and environment. In this context, a more environmentally friendly pest management strategy based on RNA interference (RNAi) has emerged as a powerful tool to control of insect pests. Here we report a successful oral RNAi in L. sativae after feeding on pak choi (Brassica rapa ssp. chinensis) that transiently express hairpin RNAs targeting vital genes in this pest. First, potentially lethal genes are identified by searching an L. sativae transcriptome for orthologs of the widely used V-ATPase A and actin genes, then expression levels are assessed during different life stages and in different adult tissues. Interestingly, the highest expression levels for V-ATPase A are observed in the adult heads (males and females) and for actin in the abdomens of adult females. We also assessed expression patterns of the target hairpin RNAs in pak choi leaves and found that they reach peak levels 72 h post agroinfiltration. RNAi-mediated knockdown of each target was then assessed by letting adult L. sativae feed on agroinfiltrated pak choi leaves. Relative transcript levels of each target gene exhibit significant reductions over the feeding time, and adversely affect survival of adult L. sativae at 24 h post infestation in genetically unmodified pak choi plants. These results demonstrate that the agroinfiltration-mediated RNAi system has potential for advancing innovative environmentally safe pest management strategies for the control of leaf-mining species.

Fast Screening of Tyrosinase Inhibitors in Coreopsis tinctoria Nutt. by Ligand Fishing Based on Paper-Immobilized Tyrosinase.

Coreopsis tinctoria Nutt. is an important medicinal plant in traditional Uyghur medicine. The skin-lightening potential of the flower has been recognized recently; however, the active compounds responsible for that are not clear. In this work, tyrosinase, a target protein for regulating melanin synthesis, was immobilized on the Whatman paper for the first time to screen skin-lightening compounds present in the flower. Quercetagetin-7-O-glucoside (1), marein (2), and okanin (3) were found to be the enzyme inhibitors. The IC50 values of quercetagetin-7-O-glucoside (1) and okanin (3) were 79.06 ± 1.08 µM and 30.25 ± 1.11 µM, respectively, which is smaller than 100.21 ± 0.11 µM of the positive control kojic acid. Enzyme kinetic analysis and molecular docking were carried out to investigate their inhibition mechanism. Although marein (2) showed a weak inhibition effect in vitro, it inhibited the intracellular tyrosinase activity and diminished melanin production in melanoma B16 cells as did the other two inhibitors. The paper-based ligand fishing method developed in this work makes it effective to quickly screen tyrosinase inhibitors from natural products. This is the first report on the tyrosinase inhibitory effect of those three compounds, showing the promising potential of Coreopsis tinctoria for the development of herbal skin-lightening products.

N-acetylgalactosaminyltransferase GALNT6 is a potential therapeutic target of clear cell renal cell carcinoma progression.

High expression of truncated O-glycans Tn antigen predicts adverse clinical outcome in patients with clear cell renal cell carcinoma (ccRCC). To understand the biosynthetic underpinnings of Tn antigen changes in ccRCC, we focused on N-acetylgalactosaminyltransferases (GALNTs, also known as GalNAcTs) known to be involved in Tn antigen synthesis. Data from GSE15641 profile and local cohort showed that GALNT6 was significantly upregulated in ccRCC tissues. The current study aimed to determine the role of GALNT6 in ccRCC, and whether GALNT6-mediated O-glycosylation aggravates malignant behaviors. Gain- and loss-of-function experiments showed that overexpression of GALNT6 accelerated ccRCC cell proliferation, migration, and invasion, as well as promoted ccRCC-derived xenograft tumor growth and lung metastasis. In line with this, silencing of GALNT6 yielded the opposite results. Mechanically, high expression of GALNT6 led to the accumulation of Tn antigen in ccRCC cells. By undertaking immunoprecipitation coupled with liquid chromatography/mass spectrometry, vicia villosa agglutinin blot, and site-directed mutagenesis assays, we found that O-glycosylation of prohibitin 2 (PHB2) at Ser161 was required for the GALNT6-induced ccRCC cell proliferation, migration, and invasion. Additionally, we identified lens epithelium-derived growth factor (LEDGF) as a key regulator of GALNT6 transcriptional induction in ccRCC growth and an upstream contributor to ccRCC aggressive behavior. Collectively, our findings indicate that GALNT6-mediated abnormal O-glycosylation promotes ccRCC progression, which provides a potential therapeutic target in ccRCC development.

Evaluation of the anti-aging potential of acetyl tripeptide-30 citrulline in cosmetics.

Acetyl tripeptide-30 citrulline, a commercialized bio-active peptide, is widely used in anti-wrinkle formulations. Volunteer-based tests have demonstrated that topical application of products containing acetyl tripeptide-30 citrulline significantly reduces the visibility of stretch marks. However, there is still a lack of research dedicated to systematically and holistically evaluating its cosmetic properties and elucidating its mechanisms of action. In this study, we assessed the cosmetic potential of acetyl tripeptide-30 citrulline using human immortalized keratinocytes (HaCaT) and mouse embryonic fibroblasts (3T3). Our findings reveal that acetyl tripeptide-30 citrulline exhibits anti-inflammatory and antioxidant activities in skin cells, particularly effective against the inflammatory markers cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), and the extent of inhibition of reactive oxygen species (ROS) production ranged from 95 % to 340 %. Moreover, acetyl tripeptide-30 citrulline specifically up-regulates Collagen IV and down-regulates matrix metalloproteinase-9 (MMP9), enhances the expression of skin barrier proteins transglutaminase 1 (TGM1) and filaggrin (FLG), thereby demonstrating its reparative capabilities. Additionally, acetyl tripeptide-30 citrulline increases the expression of the water channel protein aquaporin 3 (AQP3), thus improving skin hydration function. These results substantiate the previously proclaimed cosmetic attributes of acetyl tripeptide-30 citrulline and support its efficacy as an anti-aging agent in dermatological applications.

The molecular mechanisms underlying optical isomer arbutin permeating the skin: The molecular interaction between arbutin and skin components.

Arbutin, a typical optical isomer, has garnered widespread acclaim in the whitening cosmetics for its favorable efficacy and safety. However, the molecular mechanisms underlying α-arbutin and ß-arbutin permeating across the skin have not elucidated clearly yet. Herein we aimed to unveil how α-arbutin and ß-arbutin interacted with keratin or SC lipids, further demonstrating their relationship with their drug permeability. We found that α-arbutin displayed significantly higher drug accumulation into the porcine skin than ß-arbutin within 24 h through in vitro permeation test. Moreover, α-arbutin predominantly induced the alternations of secondary structure of amide II during the drug permeation, which was favorable for α-arbutin permeation. On the contrary, ß-arbutin exhibited an observable effect on the stretching vibration of SC lipids, possessing a significantly stronger mixing energy, binding energy and compatibility with ceramide (Cer) than that of α-arbutin, which ultimately restricted its permeation. Interestingly, free fatty acids and ceramides of the SC lipids specifically utilized its oxygen atom of carboxyl group to dock the arbutin molecules, enhancing their affinity with ß-arbutin, as confirmed by molecular simulation and 13Carbon Nuclear Magnetic Resonance. Nevertheless, a favorable compatibility between α-arbutin and keratin was observed. It was emphasized that the distinct spatial configuration and opposite optical rotation of arbutin was the leading factor impacting the intermolecular force between arbutin and the SC, and resulted in a diverse drug permeation. In cellular and in vivo skin pharmacokinetic studies, α-arbutin also possessed a higher cellular uptake and topical bioavailability than ß-arbutin. This study revealed the transdermal permeation mechanisms of optical isomer arbutin at the molecular levels, providing methodological reference for the investigations of permeation behaviors of other isomers with similar spatial configuration.

The global burden of breast cancer in women from 1990 to 2030: assessment and projection based on the global burden of disease study 2019.

Background and aim: This study aims to analyze the worldwide prevalence, mortality rates, and disability-adjusted life years (DALYs) attributed to breast cancer in women between 1990 and 2019. Additionally, it seeks to forecast the future trends of these indicators related to the burden of breast cancer in women from 2020 to 2030. Methods: Data from the Global Burden of Disease Study (GBD) 2019 was analyzed to determine the age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) of DALYs due to breast cancer in women across 204 countries and territories from 1990 to 2019. Socio-economic development levels of countries and regions were assessed using Socio-demographic Indexes, and trends in the burden of breast cancer in women worldwide from 2020 to 2030 were projected using generalized additive models (GAMs). Results: The estimated annual percentage change (EAPC) in the ASIR breast cancer in women globally was 0.36 from 1990 to 2019 and is expected to increase to 0.44 from 2020 to 2030. In 2019, the ASIR of breast cancer in women worldwide was 45.86 and is projected to reach 48.09 by 2030. The burden of breast cancer in women generally rises with age, with the highest burden expected in the 45-49 age group from 2020 to 2030. The fastest increase in burden is anticipated in Central sub-Saharan Africa (EAPC in the age-standardized death rate: 1.62, EAPC in the age-standardized DALY rate: 1.52), with the Solomon Islands (EAPC in the ASIR: 7.25) and China (EAPC in the ASIR: 2.83) projected to experience significant increases. Furthermore, a strong positive correlation was found between the ASIR breast cancer in women globally in 1990 and the projected rates for 2030 (r = 0.62). Conclusion: The anticipated increase in the ASIR of breast cancer in women globally by 2030 highlights the importance of focusing on women aged 45-49 in Central sub-Saharan Africa, Oceania, the Solomon Islands, and China. Initiatives such as breast cancer information registries, raising awareness of risk factors and incidence, and implementing universal screening programs and diagnostic tests are essential in reducing the burden of breast cancer and its associated morbidity and mortality.

Topical retinoids: Novel derivatives, nano lipid-based carriers, and combinations to improve chemical instability and skin irritation.

BACKGROUND: Retinoids, defined as synthetic or natural derivatives of vitamin A, have been extensively studied as anti-aging molecules that are widely applied in cosmetics. However, due to their physicochemical property, retinoids are highly unstable and extremely sensitive to light, oxygen, and temperature. Moreover, topical application of retinoids often leads to cutaneous irritation. These instabilities and irritant properties of retinoids limit their application in cosmetic and pharmaceutical products. AIM: Our study aimed to provide a systematic review to summarize the mechanisms underlying the instability and irritant properties of retinoids, as well as recent developments in addressing these challenges. METHODS: A comprehensive PubMed search was conducted using the following keywords: retinoids, chemical instability, skin irritation, retinoid derivatives, nano lipid-based carriers, liposomes, penetration-enhancer vesicles, ethosomes, niosomes, nanoemulsions, solid lipid nanoparticles, vitamins, soothing and hydrating agents, antioxidants and metal chelator and retinol combinations. Relevant researches published between 1968 and 2023 and studies related to these reports were reviewed. RESULTS: The development of new retinoid derivatives, the utilization of new delivery systems like nano lipid-based carriers and the combination with other compounds like vitamins, soothing agents, antioxidants and metal chelator have been explored to improve the stability, bioavailability, and toxicity of the retinoid family. CONCLUSIONS: Through advancements in formulation techniques, structure modification of retinoid derivatives and development of novel nano lipid-based carriers, the chemical instability and skin irritation of retinoids has been mitigated, ensuring their efficacy and potency over extended periods.