Safety assessment of Paeonia lactiflora root extract for a cosmetic ingredient employing the threshold of toxicological concern (TTC) approach.

Botanical extracts, widely used in cosmetics, pose a challenge to safety assessment due to their complex compositions. The threshold of toxicological concern (TTC) approach, offering a safe exposure level for cosmetic ingredients, proves to be a promising solution for ensuring the safety of cosmetic ingredients with low exposure level. We assessed the safety of Paeonia lactiflora root extract (PLR), commonly used in skin conditioning products, with the TTC. We identified 50 constituents of PLR extract from the USDA database and literature exploration. Concentration of each constituent of PLR extract was determined with the information from USDA references, literature, and experimental analysis. The genotoxicity of PLR and its constituents was assessed in vitro and in silico respectively. Cramer class of the constituents of the PLR extract was determined with Toxtree 3.1 extended decision tree using ChemTunes®. Systemic exposure of each constituent from leave-on type cosmetic products containing PLR at a 1% concentration was estimated and compared with respective TTC threshold. Two constituents exceeding TTC threshold were further analyzed for dermal absorption using in silico tools, which confirmed the safety of PLR extract in cosmetics. Collectively, we demonstrated that the TTC is a useful tool for assessing botanical extract safety in cosmetics.

Integration of the Natural Language Processing of Structural Information Simplified Molecular-Input Line-Entry System Can Improve the In Vitro Prediction of Human Skin Sensitizers.

Natural language processing (NLP) technology has recently used to predict substance properties based on their Simplified Molecular-Input Line-Entry System (SMILES). We aimed to develop a model predicting human skin sensitizers by integrating text features derived from SMILES with in vitro test outcomes. The dataset on SMILES, physicochemical properties, in vitro tests (DPRA, KeratinoSensTM, h-CLAT, and SENS-IS assays), and human potency categories for 122 substances sourced from the Cosmetics Europe database. The ChemBERTa model was employed to analyze the SMILES of substances. The last hidden layer embedding of ChemBERTa was tested with other features. Given the modest dataset size, we trained five XGBoost models using subsets of the training data, and subsequently employed bagging to create the final model. Notably, the features computed from SMILES played a pivotal role in the model for distinguishing sensitizers and non-sensitizers. The final model demonstrated a classification accuracy of 80% and an AUC-ROC of 0.82, effectively discriminating sensitizers from non-sensitizers. Furthermore, the model exhibited an accuracy of 82% and an AUC-ROC of 0.82 in classifying strong and weak sensitizers. In summary, we demonstrated that the integration of NLP of SMILES with in vitro test results can enhance the prediction of health hazard associated with chemicals.

Methylanthranilate, a Food Fragrance Attenuates Skin Pigmentation through Downregulation of Melanogenic Enzymes by cAMP Suppression.

Methyl anthranilate (MA) is a botanical fragrance used in food flavoring with unexplored potential in anti-pigment cosmetics. MA dose-dependently reduced melanin content without affecting cell viability, inhibited dendrite elongation and melanosome transfer in the co-culture system of human melanoma cells (MNT-1) and human keratinocyte cell line (HaCaT), and downregulated melanogenic genes, including tyrosinase, tyrosinase-related protein 1 and 2 (TRP-1, TRP-2). Additionally, MA decreased cyclic adenosine monophosphate (cAMP) production and exhibited a significant anti-pigmentary effect in Melanoderm™. These results suggest that MA is a promising anti-pigmentary agent for replacing or complementing existing anti-pigmentary cosmetics.

Efficacy of Allogeneic and Xenogeneic Exosomes for the Treatment of Canine Atopic Dermatitis: A Pilot Study.

Canine atopic dermatitis (CAD) is a genetically predisposed inflammatory pruritic skin disease. The available treatments for CAD have several adverse effects and vary in efficacy, indicating the need for the development of improved treatments. In this study, we aimed to elucidate the therapeutic effects of allogeneic and xenogeneic exosomes on CAD. Six laboratory beagle dogs with CAD were randomly assigned to three treatment groups: control, canine exosome (cExos), or human exosome (hExos) groups. Dogs in the cExos and hExos groups were intravenously administered 1.5 mL of cExos (5 × 1010) and hExos (7.5 × 1011) solutions, respectively, while those in the control group were administered 1.5 mL of normal saline three times per week for 4 weeks. Skin lesion score and transepidermal water loss decreased in cExos and hExos groups compared with those in the control group. The exosome treatments decreased the serum levels of inflammatory cytokines (interferon-γ, interleukin-2, interleukin-4, interleukin-12, interleukin-13, and interleukin-31) but increased those of anti-inflammatory cytokines (interleukin-10 and transforming growth factor-ß), indicating the immunomodulatory effect of exosomes. Skin microbiome analysis revealed that the exosome treatments alleviated skin bacterial dysbiosis. These results suggest that allogeneic and xenogeneic exosome therapy may alleviate CAD in dogs.

Efficient improvement of the proliferation, differentiation, and anti-arthritic capacity of mesenchymal stem cells by simply culturing on the immobilized FGF2 derived peptide, 44-ERGVVSIKGV-53.

INTRODUCTION: The stem cell microenvironment has been evidenced to robustly affect its biological functions and clinical grade. Natural or synthetic growth factors, especially, are essential for modulating stem cell proliferation, metabolism, and differentiation via the interaction with specific extracellular receptors. Fibroblast growth factor-2 (FGF-2) possesses pleiotropic functions in various tissues and organs. It interacts with the FGF receptor (FGFR) and activates FGFR signaling pathways, which involve numerous biological functions, such as angiogenesis, wound healing, cell proliferation, and differentiation. OBJECTIVES: Here, we aim to explore the molecular functions, mode of action, and therapeutic activity of yet undetermined function, FGF-2-derived peptide, FP2 (44-ERGVVSIKGV-53) in promoting the proliferation, differentiation, and therapeutic application of human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) in comparison to other test peptides, canofin1 (FP1), hexafin2 (FP3), and canofin3 (FP4) with known functions. METHODS: The immobilization of test peptides that are fused with mussel adhesive proteins (MAP) on the culture plate was carried out via EDC/NHS chemistry. Cell Proliferation assay, colony-forming unit, western blotting analysis, gene expression analysis, RNA-Seq. analysis, osteogenic, and chondrogenic differentiation capacity were applied to test the activity of the test peptides. We additionally utilized three-dimensional (3D) structural analysis and artificial intelligence (AI)-based AlphaFold2 and CABS-dock programs for receptor interaction prediction of the peptide receptor. We also verified the in vivo therapeutic capacity of FP2-cultured hWJ-MSCs using an osteoarthritis mice model. RESULTS: Culture of hWJ-MSC onto an FP2-immobilized culture plate showed a significant increase in cell proliferation (n = 3; *p < 0.05, **p < 0.01) and the colony-forming unit (n = 3; *p < 0.05, **p < 0.01) compared with the test peptides. FP2 showed a significantly upregulated phosphorylation of FRS2α and FGFR1 and activated the AKT and ERK signaling pathways (n = 3; *p < 0.05, **p < 0.01, ***p < 0.001). Interestingly, we detected efficient FP2 receptor binding that was predicted using AI-based tools. Treatment with an AKT inhibitor significantly abrogated the FP2-mediated enhancement of cell differentiation (n = 3; *p < 0.05, **p < 0.01, ***p < 0.001). Intra-articular injection of FP2-cultured MSCs significantly mitigated arthritis symptoms in an osteoarthritis mouse model, as shown through the functional tests (n = 10; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001), modulation of the expression level of the pro-inflammatory and anti-inflammatory genes, and improved osteochondral regeneration as demonstrated by tissue sections. CONCLUSION: Our study identified the FGF-2-derived peptide FP2 as a promising candidate peptide to improve the therapeutic potential of hWJ-MSCs, especially in bone and cartilage regeneration.

Skin wound healing effects of (+)-syringaresinol from ginseng berry.

Background: Ginseng has been used as a traditional medicine and functional cosmetic ingredients for many years. Recent studies have focused on the potential biological effects of the ginseng berry and its ingredients. (+)-Syringaresinol (SYR) is enriched in ginseng berry and its beneficial effects on the skin have been recently reported. However, little is known about the its effects on the wound healing process of skin. Methods: Here, we evaluated the skin wound healing effect of (+)-SYR using the human fibroblast Hs68 cell and ex vivo pig and human skin tissue model. Scratch wound test and hydrogen peroxide (HPO) induce chemical wound model were employed. Results: (+)-SYR promoted the migration and proliferation of Hs68 cells without significant cytotoxicity at the tested concentrations. Especially, in ex vivo pig and human skin tissue, HPO-induced chemical wound was recovered almost completely by (+)-SYR. In line with the finding in Hs68, the protein expression levels of TGF-ß and PCNA, a proliferation marker were increased, demonstrating the beneficial effects of (+)-SYR on skin wound repair. Conclusion: Collectively, we demonstrated that (+)-SYR from ginseng berry, can enhance the wound healing effect by accelerating cell proliferation and skin regeneration, suggesting the potential utility of (+)-SYR for skin wound repair.

Artemisia gmelinii Extract Attenuates Particulate Matter-Induced Neutrophilic Inflammation in a Mouse Model of Lung Injury.

Particulate matter (PM) induces and augments oxidative stress and inflammation, leading to respiratory diseases. Although Artemisia gmelinii Weber ex Stechm has antioxidant and anti-inflammatory effects, there are no reports on whether Artemisia gmelinii extract (AGE) regulates lung inflammation in a PM-induced model. Thus, we investigated the protective effects of AGE using a PM-induced mouse lung inflammation model. AGE significantly decreased the expression of inflammatory chemokines, neutrophil extracellular trap formation, and the total number of inflammatory cells in the bronchoalveolar lavage fluid (BALF). Furthermore, AGE attenuated lung inflammation through the suppression of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway, while promoting the nuclear factor erythroid-2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway in lung tissues. Concordant with these observations, AGE suppressed inflammatory cytokines, chemokines, reactive oxygen species, NETosis, myeloperoxidase, and neutrophil elastase by decreasing the mRNA expression of High mobility group box 1, Runt-related transcription factor 1, and Kruppel-like factor 6 in differentiated HL-60 cells. In summary, our data demonstrated that AGE suppresses PM-induced neutrophil infiltration, lung damage, and pulmonary inflammation by suppressing NF-κB/MAPK signaling pathways and enhancing the NRF2/HO-1 signaling pathway. These findings suggest that AGE administration is an effective approach for preventing and treating PM-induced respiratory inflammation.

Comparison of structural characteristics and molecular markers of rabbit skin, pig skin, and reconstructed human epidermis for an ex vivo human skin model.

The Organization for Economic Co-operation and Development approved a reconstructed human epidermis (RHE) model for in vitro skin irritation and corrosion tests as an alternative to animal testing for cosmetics, which has been banned in the European Union since 2013. However, RHE models have several limitations, such as high manufacturing costs, a loose skin barrier, and inability to simulate all cellular and non-cellular components of the human epidermis. Therefore, new alternative skin models are needed. Ex vivo skin models have been suggested as promising tools. Here, we investigated the structural similarities in the epidermis of pig and rabbit skin, a commercial RHE model (Keraskin), and human skin. To compare the structural similarity, the thickness of each epidermal layer was compared using molecular markers. Among the candidate human skin surrogates, the epidermal thickness of the pig skin was the most similar to that of human skin, followed by rabbit skin and Keraskin. Keraskin showed thicker cornified and granular layers than human skin, while rabbit skin displayed thinner layers. Moreover, the proliferation indices of Keraskin and rabbit skin were higher than those of human skin, whereas the proliferation index of the pig skin was similar to that of human skin. Some or none of the human skin barrier proteins FLG, CLDN1, and CDH1 were expressed in pig and rabbit skin, whereas all human proteins were expressed in Keraskin. Collectively, we propose ex vivo pig skin as the most suitable model for skin irritation testing because of its similarity to human skin. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00185-1.

Peroxiredoxin V Protects against UVB-Induced Damage of Keratinocytes.

Ultraviolet B (UVB) irradiation generates reactive oxygen species (ROS), which can damage exposed skin cells. Mitochondria and NADPH oxidase are the two principal producers of ROS in UVB-irradiated keratinocytes. Peroxiredoxin V (PrxV) is a mitochondrial and cytosolic cysteine-dependent peroxidase enzyme that robustly removes H2O2. We investigated PrxV's role in protecting epidermal keratinocytes against UVB-induced ROS damage. We separated mitochondrial and cytosolic H2O2 levels from other types of ROS using fluorescent H2O2 indicators. Upon UVB irradiation, PrxV-knockdown HaCaT human keratinocytes showed higher levels of mitochondrial and cytosolic H2O2 than PrxV-expressing controls. PrxV depletion enhanced hyperoxidation-mediated inactivation of mitochondrial PrxIII and cytosolic PrxI and PrxII in UVB-irradiated keratinocytes. PrxV-depleted keratinocytes exhibited mitochondrial dysfunction and were more susceptible to apoptosis through decreased oxygen consumption rate, loss of mitochondrial membrane potential, cardiolipin oxidation, cytochrome C release, and caspase activation. Our findings show that PrxV serves to protect epidermal keratinocytes from UVB-induced damage such as mitochondrial dysfunction and apoptosis, not only by directly removing mitochondrial and cytosolic H2O2 but also by indirectly improving the catalytic activity of mitochondrial PrxIII and cytosolic PrxI and PrxII. It is possible that strengthening PrxV defenses could aid in preventing UVB-induced skin damage.

Safety assessment of Cnidium officinale rhizome extract in cosmetics using the Threshold of Toxicological Concern (TTC) approach.

Cosmetics often contain botanical extracts, which present a challenge for safety assessors due to their complex composition. The threshold of toxicological concern (TTC) approach is considered as a solution for the safety assessment of botanical extracts in cosmetics as part of next-generation risk assessment. In this study, we applied the TTC approach to evaluate the safety of Cnidium officinale rhizome extract (CORE), a widely used botanical extract in skin conditioning products. We identified 32 components of CORE through the USDA database and literature and determined the content of each component through literature or actual analysis where an authentic standard was available. Macro- and micronutrients were also analyzed to exclude them as safe components. The Toxtree® software was used to identify the Cramer class of remaining components. We estimated the systemic exposure of each component from leave-on type cosmetic products containing CORE at a 1% concentration and compared the results to TTC thresholds. All components of CORE had a systemic exposure below the TTC threshold. While batch variations and presence of unknown chemicals in individual CORE materials should be considered, this study demonstrated that the TTC approach can be a useful tool for the safety assessment of botanical extracts in cosmetics.

Thermostable Human Basic Fibroblast Growth Factor (TS-bFGF) Engineered with a Disulfide Bond Demonstrates Superior Culture Outcomes in Human Pluripotent Stem Cell.

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) can differentiate into various tissues and are an essential source of various disease models and therapeutics. Various growth factors are required in order to culture pluripotent stem cells, among which basic fibroblast growth factor (bFGF) is essential for maintaining stem cell ability. However, bFGF has a short half-life (8 h) under normal mammalian cell culture conditions, and its activity decreases after 72 h, posing a serious problem in the production of high-quality stem cells. Here, we evaluated the various functions of pluripotent stem cells (PSCs) by utilizing an engineered thermostable bFGF (TS-bFGF) that is thermally stable and maintains activity longer under mammalian culture conditions. PSCs cultured with TS-bFGF showed better proliferation, stemness, morphology, and differentiation than cells cultured with wild-type bFGF. In light of the importance of stem cells in a wide range of applications in the medical and biotechnology fields, we anticipate that TS-bFGF, as a thermostable and long-acting bFGF, can play a key role in securing high-quality stem cells through various sets of stem cell culture processes.

TMBIM6-mediated miR-181a expression regulates breast cancer cell migration and invasion via the MAPK/ERK signaling pathway.

Transmembrane Bax Inhibitor Motif-containing 6 (TMBIM6) has been reported to regulate cell death pathways and is overexpressed in several types of cancers. In this study, we investigated whether high expression of TMBIM6 in breast cancer was significantly associated with cancer invasiveness. Knockdown of TMBIM6 reduced proliferation and migration of invasive breast cancer cells through downregulation of the MAPK/ERK signaling pathway. Moreover, we suggested that expression of miR-181a was significantly suppressed upon TMBIM6 knockdown. In contrast, overexpression of TMBIM6 significantly increased cell invasion and migration through up-regulation of mesenchymal markers and matrix metalloproteinase-9 (MMP-9) and enhanced activation of the MAPK/ERK signaling pathway. We also observed that up-regulation of TMBIM6 significantly increased the expression of miR-181a by TMBIM6-mediated pathway. TMBIM6 and miR-181a-mediated ERK activation induced the expression of Snail-1 and Snail-2 in FOSL-1/C-JUN-dependent manner. Overall, our data demonstrated that TMBIM6-induced miR-181a up-regulation plays an important role in the efficient modulation of migration and invasion of breast cancer cells.

Machine-learning based prediction models for assessing skin irritation and corrosion potential of liquid chemicals using physicochemical properties by XGBoost.

Skin irritation test is an essential part of the safety assessment of chemicals. Recently, computational models to predict the skin irritation draw attention as alternatives to animal testing. We developed prediction models on skin irritation/corrosion of liquid chemicals using machine learning algorithms, with 34 physicochemical descriptors calculated from the structure. The training and test dataset of 545 liquid chemicals with reliable in vivo skin hazard classifications based on UN Globally Harmonized System [category 1 (corrosive, Cat 1), 2 (irritant, Cat 2), 3 (mild irritant, Cat 3), and no category (nonirritant, NC)] were collected from public databases. After the curation of input data through removal and correlation analysis, every model was constructed to predict skin hazard classification for liquid chemicals with 22 physicochemical descriptors. Seven machine learning algorithms [Logistic regression, Naïve Bayes, k-nearest neighbor, Support vector machine, Random Forest, Extreme gradient boosting (XGB), and Neural net] were applied to ternary and binary classification of skin hazard. XGB model demonstrated the highest accuracy (0.73-0.81), sensitivity (0.71-0.92), and positive predictive value (0.65-0.81). The contribution of physicochemical descriptors to the classification was analyzed using Shapley Additive exPlanations plot to provide an insight into the skin irritation of chemicals. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-022-00168-8.

Ductal delivery of extracellular vesicles promote the recovery from salivary gland inflammation.

Salivary gland dysfunction worsens the quality of life, but treatment for restoration of salivary gland function is limited. Although previous reports have demonstrated the therapeutic potentials of extracellular vesicles (EVs) in different preclinical models, the role of EVs in salivary glands remains elusive. Furthermore, little is known about the roles of salivary gland-derived EVs in tissue repair or regeneration compared to other EVs. In this study, EVs secreted from salivary gland-derived mesenchymal stem cells (sgMSCs) were comparatively analyzed with those from Wharton's jelly-derived MSC (wjMSCs). sgMSCs secreted more significant amounts of EVs than wjMSCs, and salivary gland epithelial cells showed a more efficient uptake of sgMSC-EVs than wjMSC-EVs. The possibility of immune regulation was tested via macrophage polarization and LPS-induced epithelial inflammation, resulting in an M1-to-M2 shift and reversal of acinar-to-ductal metaplasia by sgMSC-EV. Furthermore, the roles of sgMSC-EV-mediated immune regulation and tissue repair were clarified in vivo via retroductal delivery of sgMSC-EVs in a mouse model of obstructive sialadenitis. Collectively, our data demonstrate the superior role of sgMSC-EVs in the recovery from salivary gland inflammation and injury and suggest EVs as therapeutic tools for salivary gland dysfunction.

Improved Wound Healing and Skin Regeneration Ability of 3,2'-Dihydroxyflavone-Treated Mesenchymal Stem Cell-Derived Extracellular Vesicles.

Flavonoids enhance the self-renewal and differentiation potential of mesenchymal stem cells (MSCs) and have therapeutic activities, including regenerative, anti-oxidative, and anti-inflammatory effects. Recent studies have revealed that MSC-derived extracellular vesicles (MSC-EVs) have therapeutic effects on tissue regeneration and inflammation. To facilitate further research on the therapeutic potential of MSC-EVs derived from flavonoid-treated MSCs, we surveyed the production of EVs and their therapeutic applications in wound regeneration. MSCs treated with flavonoids enhanced EV production twofold compared with naïve MSCs. EVs produced by MSCs treated with flavonoids (Fla-EVs) displayed significant anti-inflammatory and wound-healing effects in vitro. The wound-healing capacity of EVs was mediated by the upregulation of mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling. Interestingly, the protein level of p-ERK under inhibition of MEK signals was maintained in Fla-EV-treated fibroblasts, suggesting that Fla-EVs have a higher therapeutic potential than naïve MSC-EVs (Cont-EVs) in wound healing. Moreover, the in vivo wound closure effect of the Fla-EVs showed significant improvement compared with that of the flavonoid-only treatment group and the Cont-EVs. This study provides a strategy for the efficient production of EVs with superior therapeutic potential using flavonoids.

Bulb of Lilium longiflorum Thunb Extract Fermented with Lactobacillus acidophilus Reduces Inflammation in a Chronic Obstructive Pulmonary Disease Model.

Chronic obstructive pulmonary disease (COPD), one of the leading causes of death worldwide, is caused by repeated exposure to harmful matter, such as cigarette smoke. Although Lilium longiflorum Thunb (LLT) has anti-inflammatory effects, there is no report on the fermented LLT bulb extract regulating lung inflammation in COPD. Thus, we investigated the protective effect of LLT bulb extract fermented with Lactobacillus acidophilus 803 in COPD mouse models induced by cigarette smoke extract (CSE) and porcine pancreas elastase (PPE). Oral administration of the fermented product (LS803) suppressed the production of inflammatory mediators and the infiltration of immune cells involving neutrophils and macrophages, resulting in protective effects against lung damage. In addition, LS803 inhibited CSE- and LPS-induced IL-6 and IL-8 production in airway epithelial H292 cells as well as suppressed PMA-induced formation of neutrophil extracellular traps in HL-60 cells. In particular, LS803 significantly repressed the elevated IL-6 and MIP-2 production after CSE and LPS stimulation by suppressing the activity of the nuclear factor kappa-light-chain-enhancer of activated B (NFκB) in mouse peritoneal macrophages. Therefore, our results suggest that the fermented product LS803 is effective in preventing and alleviating lung inflammation.

Multilamellar ceramide core-structured microvehicles with substantial skin barrier function recovery.

This study introduces a multilamellar ceramide core-structured microvehicle platform for substantial skin barrier function recovery. Our approach essentially focused on fabricating bacterial cellulose nanofiber (BCNF)-enveloped ceramide-rich lipid microparticles (CerMPs) by solidifying BCNF-armored oil-in-water Pickering emulsions. The oil drops consisted of Ceramide NP (a phytosphingosine backbone N-acylated with a saturated stearic acid) and fatty alcohols (FAs) with a designated stoichiometry. The thin BCNF shell layer completely blocked the growth of ceramide molecular crystals from the CerMPs for a long time. The CerMP cores displayed a multilamellar structure wherein the interlayer distance and lateral packing could be manipulated using FAs with different alkyl chain lengths. The CerMPs remarkably lowered the trans-epidermal water loss while restoring the structural integrity of the epidermis in damaged skin. The results obtained herein highlight that the CerMP system provides a practical methodology for developing various types of skin-friendly formulations that can strengthen the skin barrier function.

Bioactive peptides for boosting stem cell culture platform: Methods and applications.

Peptides, short protein fragments, can emulate the functions of their full-length native counterparts. Peptides are considered potent recombinant protein alternatives due to their specificity, high stability, low production cost, and ability to be easily tailored and immobilized. Stem cell proliferation and differentiation processes are orchestrated by an intricate interaction between numerous growth factors and proteins and their target receptors and ligands. Various growth factors, functional proteins, and cellular matrix-derived peptides efficiently enhance stem cell adhesion, proliferation, and directed differentiation. For that, peptides can be immobilized on a culture plate or conjugated to scaffolds, such as hydrogels or synthetic matrices. In this review, we assess the applications of a variety of peptides in stem cell adhesion, culture, organoid assembly, proliferation, and differentiation, describing the shortcomings of recombinant proteins and their full-length counterparts. Furthermore, we discuss the challenges of peptide applications in stem cell culture and materials design, as well as provide a brief outlook on future directions to advance peptide applications in boosting stem cell quality and scalability for clinical applications in tissue regeneration.

The Orphan GPR50 Receptor Regulates the Aggressiveness of Breast Cancer Stem-like Cells via Targeting the NF-kB Signaling Pathway.

The expression of GPR50 in CSLC and several breast cancer cell lines was assessed by RT-PCR and online platform (UALCAN, GEPIA, and R2 gene analysis). The role of GPR50 in driving CSLC, sphere formation, cell proliferation, and migration was performed using shGPR50 gene knockdown, and the role of GPR50-regulated signaling pathways was examined by Western blotting and Luciferase Assay. Herein, we confirmed that the expression of G protein-coupled receptor 50 (GPR50) in cancer stem-like cells (CSLC) is higher than that in other cancer cells. We examined that the knockdown of GPR50 in CSLC led to decreased cancer properties, such as sphere formation, cell proliferation, migration, and stemness. GPR50 silencing downregulates NF-kB signaling, which is involved in sphere formation and aggressiveness of CSLC. In addition, we demonstrated that GPR50 also regulates ADAM-17 activity by activating NOTCH signaling pathways through the AKT/SP1 axis in CSLC. Overall, we demonstrated a novel GPR50-mediated regulation of the NF-κB-Notch signaling pathway, which can provide insights into CSLC progression and prognosis, and NF-κB-NOTCH-based CSLC treatment strategies.

Tiered human health risk assessment of antibacterial quaternary ammonium compounds (QACs) in dishwashing detergents.

Quaternary ammonium compounds (QACs) are widely used in consumer products because of their unique antibacterial properties, and dishwashing detergents are a major source of exposure through oral, inhalation, and dermal routes. The three classes of QACs, including benzalkonium chloride (BAC), n-alkyldimethylethylbenzylammonium chloride (ADEBAC), and di-n-alkyldimethylammonium chloride (DDAC), in spray and non-spray types of dishwashing detergents were quantified by high-performance liquid chromatography-mass spectrometry. A tiered risk assessment approach was also considered. In the Tier 1 assessment, the mean and worst-case exposure were estimated to screen for rough exposure and risk levels. In the Tier 2 assessment, mean and upper-tail exposure levels were calculated based on the exposure parameters of Korean consumers using Monte Carlo simulation. QACs had a low frequency of detection of up to 20% in dishwashing detergents, and the contents of detected QACs varied depending on the individual samples. Based on the results of the Tier 1 assessment, BACs and DDACs posed potential health risks via inhalation and dermal routes. Tier 2 assessment suggested that the current level of oral and dermal exposure of Korean consumers to QACs in dishwashing detergents is unlikely to pose a health risk, even for upper-tail exposure groups. However, the present results suggest that spray-type DDACs may pose a health risk in the upper-tail inhalation exposure group, and further investigation is required to clarify this risk.