Tricholoma matsutake polysaccharides suppress excessive melanogenesis via JNK-mediated pathway: Investigation in 8- methoxypsoralen induced B16-F10 melanoma cells and clinical study.

Skin hyperpigmentation is a worldwide condition associated with augmented melanogenesis. However, conventional therapies often entail various adverse effects. Here, we explore the safety range and depigmentary effects of polysaccharides extract of Tricholoma matsutake (PETM) in an in vitro model and further evaluated its efficacy at the clinical level. An induced-melanogenesis model was established by treating B16-F10 melanoma cells with 8-methoxypsoralen (8-MOP). Effects of PETM on cell viability and melanin content were examined and compared to a commonly used depigmentary agent, α-arbutin. Expressions of key melanogenic factors and upstream signaling pathway were analysed by quantitative PCR and western blot. Moreover, a placebo-controlled clinical study involving Chinese females with skin hyperpigmentation was conducted to measure the efficacy of PETM on improving facial pigmented spots, melanin index, and individual typology angle (ITA°). Results demonstrated that PETM (up to 0.5 mg/mL) had little effect on the viability and motility of B16-F10 cells. Notably, it significantly suppressed the melanin content and expressions of key melanogenic factors induced by 8-MOP in B16-F10 melanoma cells. Western blotting results revealed that PETM inhibited melanogenesis by inactivating c-Jun N-terminal kinase (JNK), and this inhibitory role could be rescued by JNK agonist treatment. Clinical findings showed that PETM treatment resulted in a significant reduction of facial hyperpigmented spot, decreased melanin index, and improved ITA° value compared to the placebo-control group. In conclusion, these in vitro and clinical evidence demonstrated the safety and depigmentary efficacy of PETM, a novel polysaccharide agent. The distinct mechanism of action of PETM on melanogenic signaling pathway positions it as a promising agent for developing alternative therapies.

Orientation-dependent oxidation behavior of Cu under In-situ E-Beam irradiation.

Herein, we present an atomic in-situ investigation of Cu oxidation along different orientations stimulated by high-energy electron beams (E-Beam) in transmission electron microscopy (TEM). By following the microstructural evolution of the Cu substrate in real time, high-resolution TEM (HRTEM) images reveal an orientation-dependent oxidation mechanism, whereby Cu along [110] zone axis migrates onto the surface and be oxidized while Cu along [100] zone axis is oxidized completely both in bulk and at the surface. The different oxidation mechanisms can be attributed to the differing diffusion rates of oxygen in Cu structures along directions. Moreover, the growth of Cu oxides is found to follow a layer-by-layer mechanism, where Cu mostly migrates onto nanocrystal {110} planes. This behavior would lead to the oxides wider in geometric shape and therefore promote the aggregation of adjacent oxides. These findings have important implications for the practical use of copper-based materials in oxidizing environments.

Rhizoma Paridis saponins attenuate Gram-negative bacteria-induced inflammatory acne by binding to KEAP1 and modulating Nrf2 and MAPK pathways.

Acne vulgaris represents a chronic inflammatory condition, the pathogenesis of which is closely associated with the altered skin microbiome. Recent studies have implicated a profound role of Gram-negative bacteria in acne development, but there is a lack of antiacne agents targeting these bacteria. Polyphyllins are major components of Rhizoma Paridis with great anti-inflammatory potential. In this study, we aimed to evaluate the antiacne effects and the underlying mechanisms of PPH and a PPH-enriched Rhizoma Paridis extract (RPE) in treating the Gram-negative bacteria-induced acne. PPH and RPE treatments significantly suppressed the mRNA and protein expressions of interleukin (IL)-1ß and IL-6 in lipopolysaccharide (LPS)-induced RAW 264.7 and HaCaT cells, along with the intracellular reactive oxygen species (ROS) generation. Furthermore, PPH and RPE inhibited the nuclear translocation of nuclear factor kappa-B (NF-κB) P65 in LPS-induced RAW 264.7 cells. Based on molecular docking, PPH could bind to kelch-like ECH-associated protein 1 (KEAP1) protein. PPH and RPE treatments could activate nuclear factor erythroid 2-related factor 2 (NRF2) and upregulate haem oxygenase-1 (HO-1). Moreover, RPE suppressed the mitogen-activated protein kinase (MAPK) pathway. Therefore, PPH-enriched RPE showed anti-inflammatory and antioxidative effects in vitro, which is promising for alternative antiacne therapeutic.

Structuring and Shaping of Mechanically Robust and Functional Hydrogels toward Wearable and Implantable Applications.

Hydrogels possess unique features such as softness, wetness, responsiveness, and biocompatibility, making them highly suitable for biointegrated applications that have close interactions with living organisms. However, conventional man-made hydrogels are usually soft and brittle, making them inferior to the mechanically robust biological hydrogels. To ensure reliable and durable operation of biointegrated wearable and implantable devices, mechanical matching and shape adaptivity of hydrogels to tissues and organs are essential. Recent advances in polymer science and processing technologies have enabled mechanical engineering and shaping of hydrogels for various biointegrated applications. In this review, polymer network structuring strategies at micro/nanoscales for toughening hydrogels are summarized, and representative mechanical functionalities that exist in biological materials but are not easily achieved in synthetic hydrogels are further discussed. Three categories of processing technologies, namely, 3D printing, spinning, and coating for fabrication of tough hydrogel constructs with complex shapes are reviewed, and the corresponding hydrogel toughening strategies are also highlighted. These developments enable adaptive fabrication of mechanically robust and functional hydrogel devices, and promote application of hydrogels in the fields of biomedical engineering, bioelectronics, and soft robotics.

Developmental validation of the STRSeqTyper122 kit for massively parallel sequencing of forensic STRs.

Massively parallel sequencing allows for integrated genotyping of different types of forensic markers, which reduces DNA consumption, simplifies experimental processes, and provides additional sequence-based genetic information. The STRseqTyper122 kit genotypes 63 autosomal STRs, 16 X-STRs, 42 Y-STRs, and the Amelogenin locus. Amplicon sizes of 117 loci were below 300 bp. In this study, MiSeq FGx sequencing metrics for STRseqTyper122 were presented. The genotyping accuracy of this kit was examined by comparing to certified genotypes of NIST standard reference materials and results from five capillary electrophoresis-based kits. The sensitivity of STRseqTyper122 reached 125 pg, and > 80% of the loci were correctly called with 62.5 pg and 31.25 pg input genomic DNA. Repeatability, species specificity, and tolerance for DNA degradation and PCR inhibitors of this kit were also evaluated. STRseqTyper122 demonstrated reliable performance with routine case-work samples and provided a powerful tool for forensic applications.

Tailored Polypyrrole Nanofibers as Ion-to-Electron Transduction Membranes for Wearable K+ Sensors.

Conductive polymers are recognized as ideal candidates for the development of noninvasive and wearable sensors for real-time monitoring of potassium ions (K+ ) in sweat to ensure the health of life. However, the low ion-to-electron transduction efficiency and limited active surface area hamper the development of high-performance sensors for low-concentration K+ detection in the sweat. Herein, a wearable K+ sensor is developed by tailoring the nanostructure of polypyrrole (PPy), serving as an ion-to-electron transduction layer, for accurately and stably tracing the K+ fluctuation in human sweat. The PPy nanostructures can be tailored from nanospheres to nanofibers by controlling the supramolecular assembly process during PPy polymerization. Resultantly, the ion-to-electron transduction efficiency (17-fold increase in conductivity) and active surface area (1.3-fold enhancement) are significantly enhanced, accompanied by minimized water layer formation. The optimal PPy nanofibers-based K+ sensor achieved a high sensitivity of 62 mV decade-1 , good selectivity, and solid stability. After being integrated with a temperature sensor, the manufactured wearable sensor realized accurate monitoring of K+ fluctuation in the human sweat.

Uncovering the Anti-Angiogenic Mechanisms of Centella asiatica via Network Pharmacology and Experimental Validation.

BACKGROUND: Centella asiatica (CA) has been used to address cancer for centuries in traditional Chinese medicine (TCM). Previous studies demonstrated its anti-angiogenesis efficacy, but the underlying mechanism of its action remains to be further clarified. This study aims to investigate the underlying mechanisms of CA and its triterpenes in anti-angiogenesis for cancer therapeutics through network pharmacology and experimental validation. METHODS: Cytoscape was used to construct a network of compound-disease targets and protein-protein interactions (PPIs) from which core targets were identified. GO and KEGG analyses were performed using Metascape, and the AutoDock-Vina program was used to realize molecular docking for further verification. Then, VEGF165 was employed to establish an induced angiogenesis model. The anti-angiogenic effects of CA were evaluated through assays measuring cell proliferation, migration, and tubular structure formation. RESULTS: Twenty-five active ingredients in CA had potential targets for anti-angiogenesis including madecassoside, asiaticoside, madecassic acid, asiatic acid, and asiaticoside B. In total, 138 potential targets for CA were identified, with 19 core targets, including STAT3, SRC, MAPK1, and AKT1. A KEGG analysis showed that CA is implicated in cancer-related pathways, specifically PD-1 and AGE-RAGE. Molecular docking verified that the active components of CA have good binding energy with the first four important targets of angiogenesis. In experimental validation, the extracts and triterpenes of CA improved VEGF165-induced angiogenesis by reducing the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). CONCLUSIONS: Our results initially demonstrate the effective components and great anti-angiogenic activity of CA. Evidence of the satisfactory anti-angiogenic action of the extracts and triterpenes from CA was verified, suggesting CA's significant potential as a prospective agent for the therapy of cancer.

Dormancy and double-activation strategy for construction of high-performance mixed-matrix membranes.

Mixed-matrix membranes (MMMs) have the potential for energy-efficient gas separation by matching the superior mass transfer and anti-plasticization properties of the fillers with processability and scaling up features of the polymers. However, construction of high-performance MMMs has been prohibited due to low filler-loading and the existence of interfacial defects. Here, high MOF-loaded, i.e., 55 wt %, MMMs are developed by a 'dormancy and double-activation' (DDA) strategy. High MOF precursor concentration suppresses crystallization in the membrane casting solution, realizing molecular level mixing of all components. Then, the polymeric matrix was formed with uniform encapsulation of MOF nutrients. Subsequently, double-activation was employed to induce MOF crystallization: the alkali promotes MOFs nucleation to harvest small porous nanocrystals while excessive ligands activate the metal ions to enhance the MOFs conversion. As such, quasi-semi-continuous mass transfer channels can be formed in the MMMs by the connected MOFs nanocrystals to boost the gas permeability. The optimized MMM shows significantly ameliorated CO2 permeability, i.e., 2841 Barrer, five-fold enhancement compared with pristine polymer membrane, with a good CO2 /N2 selectivity of 36. Besides, the nanosized MOFs intensify their interaction with polymer chains, endowing the MMMs with good anti-plasticization behaviour and stability, which advances practical application of MMMs in carbon capture.

Effect of SARS-CoV-2 infection on semen parameters in sperm bank volunteers with normal sperm concentration.

In this study, we aimed to assess the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on semen parameters. The study comprised 110 sperm volunteers who self-reported SARS-CoV-2 infection from the Human Sperm Bank of the Center for Reproductive Medicine, Shandong University (Jinan, China). The volunteers had normal sperm concentration before infection. Each volunteer provided semen samples before and after infection. We selected 90 days after infection as the cutoff point. Semen parameters within 90 days after infection of 109 volunteers (group A) were compared with semen parameters before infection. Moreover, semen parameters on or after 90 days after infection of 36 volunteers (group B) were compared with semen parameters before infection. Furthermore, based on whether the volunteers had completed the three-dose SARS-CoV-2 vaccination booster, volunteers in group A and B were further divided into two subgroups separately. Semen parameters were compared before and after infection in each subgroup. Our results showed that in this cohort population, the semen quality in volunteers with normal sperm concentrations before infection decreased after SARS-CoV-2 infection within 90 days, while the semen quality returned to preinfection levels after 90 days. The completion of a three-dose SARS-CoV-2 vaccination booster may exert a protective effect on semen quality after infection.

Long non-coding RNA PRR7-AS1 promotes osteosarcoma progression via binding RNF2 to transcriptionally suppress MTUS1.

Introduction: Osteosarcoma is a common bone malignant tumor in adolescents with high mortality and poor prognosis. At present, the progress of osteosarcoma and effective treatment strategies are not clear. This study provides a new potential target for the progression and treatment of osteosarcoma. Methods: The relationship between lncRNA PRR7-AS1 and osteosarcoma was analyzed using the osteosarcoma databases and clinical sample testing. Cell function assays and tumor lung metastasis were employed to study the effects of PRR7-AS1 on tumorigenesis in vivo and in vitro. Potential downstream RNF2 of PRR7-AS1 was identified and explored using RNA pulldown and RIP. The GTRD and KnockTF database were used to predict the downstream target gene, MTUS1, and ChIP-qPCR experiments were used to verify the working mechanismy. Rescue experiments were utilized to confirm the role of MTUS1 in the pathway. Results: Deep mining of osteosarcoma databases combined with clinical sample testing revealed a positive correlation between lncRNA PRR7-AS1 and osteosarcoma progression. Knockdown of PRR7-AS1 inhibited osteosarcoma cell proliferation and metastasis in vitro and in vivo. Mechanistically, RNA pulldown and RIP revealed that PRR7-AS1 may bind RNF2 to play a cancer-promoting role. ChIP-qPCR experiments were utilized to validate the working mechanism of the downstream target gene MTUS1. RNF2 inhibited the transcription of MTUS1 through histone H2A lysine 119 monoubiquitin. Rescue experiments confirmed MTUS1 as a downstream direct target of PRR7-AS1 and RNF2. Discussion: We identified lncRNA PRR7-AS1 as an important oncogene in osteosarcoma progression, indicating that it may be a potential target for diagnosis and prognosis of osteosarcoma.

Developmental validation of a high-resolution panel genotyping 639 Y-chromosome SNP and InDel markers and its evolutionary features in Chinese populations.

Uniparental-inherited haploid genetic marker of Y-chromosome single nucleotide polymorphisms (Y-SNP) have the power to provide a deep understanding of the human evolutionary past, forensic pedigree, and bio-geographical ancestry information. Several international cross-continental or regional Y-panels instead of Y-whole sequencing have recently been developed to promote Y-tools in forensic practice. However, panels based on next-generation sequencing (NGS) explicitly developed for Chinese populations are insufficient to represent the Chinese Y-chromosome genetic diversity and complex population structures, especially for Chinese-predominant haplogroup O. We developed and validated a 639-plex panel including 633 Y-SNPs and 6 Y-Insertion/deletions, which covered 573 Y haplogroups on the Y-DNA haplogroup tree. In this panel, subgroups from haplogroup O accounted for 64.4% of total inferable haplogroups. We reported the sequencing metrics of 354 libraries sequenced with this panel, with the average sequencing depth among 226 individuals being 3,741×. We illuminated the high level of concordance, accuracy, reproducibility, and specificity of the 639-plex panel and found that 610 loci were genotyped with as little as 0.03 ng of genomic DNA in the sensitivity test. 94.05% of the 639 loci were detectable in male-female mixed DNA samples with a mix ratio of 1:500. Nearly all of the loci were genotyped correctly when no more than 25 ng/µL tannic acid, 20 ng/µL humic acid, or 37.5 µM hematin was added to the amplification mixture. More than 80% of genotypes were obtained from degraded DNA samples with a degradation index of 11.76. Individuals from the same pedigree shared identical genotypes in 11 male pedigrees. Finally, we presented the complex evolutionary history of 183 northern Chinese Hans and six other Chinese populations, and found multiple founding lineages that contributed to the northern Han Chinese gene pool. The 639-plex panel proved an efficient tool for Chinese paternal studies and forensic applications.

Comparison for the simultaneous determination of 237Np and Pu isotopes between TEVA and TK200 resin.

A reliable and stable method was developed to accurately analyze neptunium (237Np) and plutonium isotopes in environmental samples using 242Pu or 236Pu as a tracer. Key parameters, including the valence adjustment conditions and the stabilities of Pu and Np in the different resins, were investigated using TK200 and TEVA resin. It was found that Pu and Np could be efficiently extracted simultaneously using TK200 resin under the optimal loading conditions (6-12 M HNO3) with the addition of 0.01-0.12 M NaNO2 for valence adjustment. These isotopes were subsequently stripped out using a solution containing 0.1 M HCl, 0.05 M HF, and 0.01 M NH2OH·HCl. The separation efficiencies of Pu and Np were >93%, and the chemical yield ratio between Np and Pu was maintained steady at an average of 1.00 ± 0.03 (n > 50) under the optimal conditions. The analytical method was validated by analyzing environmental soil samples spiked with known amounts of 239Pu and 237Np standard solutions or certified reference materials. The measured values of 237Np, 239Pu, and 240Pu obtained by inductively coupled plasma tandem mass spectrometry were consistent with their International Atomic Energy Agency literature values within a 95% confidence interval. These results confirm the reliability and high analytical precision (<6%) of this developed method using Pu as a non-isotopic tracer for monitoring the chemical yield of 237Np. The developed method can also be used for environmental pollutant monitoring and for tracer studies of the 237Np and Pu isotopes.

Engineer Nanoscale Defects into Selective Channels: MOF-Enhanced Li+ Separation by Porous Layered Double Hydroxide Membrane.

Two-dimensional (2D) membrane-based ion separation technology has been increasingly explored to address the problem of lithium resource shortage, yet it remains a sound challenge to design 2D membranes of high selectivity and permeability for ion separation applications. Zeolitic imidazolate framework functionalized modified layered double hydroxide (ZIF-8@MLDH) composite membranes with high lithium-ion (Li+) permeability and excellent operational stability were obtained in this work by in situ depositing functional ZIF-8 nanoparticles into the nanopores acting as framework defects in MLDH membranes. The defect-rich framework amplified the permeability of Li+, and the site-selective growth of ZIF-8 in the framework defects bettered its selectivity. Specifically speaking, the ZIF-8@MLDH membranes featured a high permeation rate of Li+ up to 1.73 mol m-2 h-1 and a desirable selectivity of Li+/Mg2+ up to 31.9. Simulations supported that the simultaneously enhanced selectivity and permeability of Li+ are attributed to changes in the type of mass transfer channels and the difference in the dehydration capacity of hydrated metal cations when they pass through nanochannels of ZIF-8. This study will inspire the ongoing research of high-performance 2D membranes through the engineering of defects.

Uranium uptake is mediated markedly by clathrin-mediated endocytosis and induce dose-dependent toxicity in HK-2 cells.

The objective of this study was to explore the endocytosis mechanisms of uranium uptake in HK-2 cells and its toxic effects. Our results demonstrated that uranium exposure impairs redox homeostasis and increases the permeability of the cell membrane and mitochondrial membrane, which may induce cell apoptosis by cytochrome-c leakage. Alkaline phosphatase activity increased after uranium exposure, which may be involved in the process of intracellular mineralisation of uranium, leading to severe cell necrosis. Furthermore, our findings demonstrated that the clathrin-mediated endocytosis process contributed substantially to uranium uptake in HK-2 cells and the total uranium uptake was highly correlated with cell viability, reaching a high correlation coefficient (r = -0.853) according to Pearson correlation analysis. In conclusion, the uptake of uranium into mammalian cells was mainly facilitated by the clathrin-mediated endocytosis pathway and induced dose-dependent cellular toxicity, including redox homeostasis imbalance, membrane injury, cell apoptosis and necrosis.

Microstructure optimization of bioderived polyester nanofilms for antibiotic desalination via nanofiltration.

The successful implementation of thin-film composite membranes (TFCM) for challenging solute-solute separations in the pharmaceutical industry requires a fine control over the microstructure (size, distribution, and connectivity of the free-volume elements) and thickness of the selective layer. For example, desalinating antibiotic streams requires highly interconnected free-volume elements of the right size to block antibiotics but allow the passage of salt ions and water. Here, we introduce stevioside, a plant-derived contorted glycoside, as a promising aqueous phase monomer for optimizing the microstructure of TFCM made via interfacial polymerization. The low diffusion rate and moderate reactivity of stevioside, together with its nonplanar and distorted conformation, produced thin selective layers with an ideal microporosity for antibiotic desalination. For example, an optimized 18-nm membrane exhibited an unprecedented combination of high water permeance (81.2 liter m-2 hour-1 bar-1), antibiotic desalination efficiency (NaCl/tetracycline separation factor of 11.4), antifouling performance, and chlorine resistance.

Detection of Carbamazepine and Its Metabolites in Blood Samples by LC-MS/MS.

OBJECTIVES: To establish a method for the detection of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: The blood samples were treated with 1-butyl-3-methylimidazolium hexafluorophosphate as an extraction solvent. The samples were extracted by ultrasound-assisted extraction and separated by ZORBAX Eclipse Plus C18, 95Å column. The mobile phase A aqueous solution containing 0.1% formic acid and 10 mmol/L ammonium acetate, and mobile phase B mixed organic solvent containing acetonitrile/methanol (Vacetonitrile∶Vmethanol=2∶3) were used for gradient elution at the flow rate of 1.00 mL/min. An electrospray ion source in positive mode was used for detection in the multiple reaction monitoring. RESULTS: The linearities of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples were good within the corresponding range, with correlation coefficients (r) greater than 0.995 6. The limits of detection were 3.00, 0.40 and 1.30 ng/mL, respectively. The limit of quantitation were 8.00, 1.00 and 5.00 ng/mL, respectively. The extraction recoveries ranged from 76.00% to 106.44%. The relative standard deviations of the intra-day and inter-day precisions were less than 16%. Carbamazepine and its main metabolite 10,11-dihydro-10,11-epoxycarbamazepine were detected in blood samples of death cases with a mass concentration of 2.71 µg/mL and 252.14 ng/mL, respectively. CONCLUSIONS: This method has high sensitivity and good selectivity, which is suitable for the detection of carbamazepine and its metabolites in blood samples, and can be used for carbamazepine-related forensic identifications.

Micro/Nano-Fabrication of Flexible Poly(3,4-Ethylenedioxythiophene)-Based Conductive Films for High-Performance Microdevices.

With the increasing demands for novel flexible organic electronic devices, conductive polymers are now becoming the rising star for reaching such targets, which has witnessed significant breakthroughs in the fields of thermoelectric devices, solar cells, sensors, and hydrogels during the past decade due to their outstanding conductivity, solution-processing ability, as well as tailorability. However, the commercialization of those devices still lags markedly behind the corresponding research advances, arising from the not high enough performance and limited manufacturing techniques. The conductivity and micro/nano-structure of conductive polymer films are two critical factors for achieving high-performance microdevices. In this review, the state-of-the-art technologies for developing organic devices by using conductive polymers are comprehensively summarized, which will begin with a description of the commonly used synthesis methods and mechanisms for conductive polymers. Next, the current techniques for the fabrication of conductive polymer films will be proffered and discussed. Subsequently, approaches for tailoring the nanostructures and microstructures of conductive polymer films are summarized and discussed. Then, the applications of micro/nano-fabricated conductive films-based devices in various fields are given and the role of the micro/nano-structures on the device performances is highlighted. Finally, the perspectives on future directions in this exciting field are presented.

Facile Fabrication of a Continuous ZIF-67 Membrane for Efficient Azeotropic Organic Solvent Mixture Separation.

Azeotropic organic solvent mixture separation is common in the chemical industry but extremely difficult. Zeolitic imidazolate framework-67 (ZIF-67) shows great potential in organic solvent mixture separation due to its rigid micropores and excellent stability. However, due to the fast nucleation rate, it is a great challenge to prepare continuous ZIF-67 membrane layers with ultrathin thickness. In this study, a hydroxy salt layer with high inducible activity was synthesized as a precursor on different porous substrates to prepare ZIF-67 membranes at room temperature. The precursor layer enables an intact ZIF-67 membrane with an ultrathin thickness of 176±12 nm. The experimental and simulation results confirmed that the size sieving through the pore windows and the preferential adsorption of polar solvent molecules provide the ZIF-67 membrane an unprecedented separation performance such as high separation factors and fluxes, for four types of azeotropic organic solvent mixtures.

Role of PI3K-AKT Pathway in Ultraviolet Ray and Hydrogen Peroxide-Induced Oxidative Damage and Its Repair by Grain Ferments.

UV and external environmental stimuli can cause oxidative damage to skin cells. However, the molecular mechanisms involved in cell damage have not been systematically and clearly elucidated. In our study, an RNA-seq technique was used to determine the differentially expressed genes (DEGs) of the UVA/H2O2-induced model. Gene Oncology (GO) clustering and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis were performed to determine the core DEGs and key signaling pathway. The PI3K-AKT signaling pathway was selected as playing a part in the oxidative process and was verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We selected three kinds of Schizophyllum commune fermented actives to evaluate whether the PI3K-AKT signaling pathway also plays a role in the resistance of active substances to oxidative damage. Results indicated that DEGs were mainly enriched in five categories: external stimulus response, oxidative stress, immunity, inflammation, and skin barrier regulation. S. commune-grain ferments can effectively reduce cellular oxidative damage through the PI3K-AKT pathway at both the cellular and molecular levels. Some typical mRNAs (COL1A1, COL1A2, COL4A5, FN1, IGF2, NR4A1, and PIK3R1) were detected, and the results obtained were consistent with those of RNA-seq. These results may give us a common set of standards or criteria for the screen of anti-oxidative actives in the future.

Aloe Extracts Inhibit Skin Inflammatory Responses by Regulating NF-κB, ERK, and JNK Signaling Pathways in an LPS-Induced RAW264.7 Macrophages Model.

Introduction: Inflammation generally refers to the body's defensive response to stimuli, and skin inflammation is still one of the major problems that affect human physical and mental health. While current pharmacological treatments are reported to have cytotoxicity and various side effects, herbal medicines with few side effects and low cytotoxicity are considered as alternative therapeutic approaches. Methods: In order to investigate anti-inflammatory effects and mechanisms of ALOE, the potential cytotoxicity of A. vera extracts (ALOE) was determined in vitro at first. The production of the pro-inflammatory proteins (ie, IL-6, TNF-α) in lipopolysaccharides (LPS) and ultraviolet A (UVA)-stimulated HaCaT and RAW264.7 cells were then treated with ALOE to test its inhibitory effects using enzyme-linked immunosorbent assay (ELISA). To further explore the anti-inflammatory mechanisms of ALOE, quantitative Polymerase Chain Reaction (qPCR) was used to analyze the mRNA expression of inflammatory genes iNOS, COX-2 and NO production. For NF-κB and MAPK signaling pathways analysis, Western blotting and nuclear fluorescence staining were used to evaluate the expression of key factors. Results: ALOE did not exhibit obvious cytotoxicity (0-3 mg/mL) in vitro. ALOE was able to inhibit the expression of pro-inflammatory cytokines IL-6, TNF-α and functioned more prominently in LPS-induced model. ALOE could also suppress the mRNA expression of LPS-induced iNOS and COX-2 and further down-regulate NO level. Furthermore, ALOE reduced the protein expression of P65 in NF-κB signaling pathway and suppressed LPS-induced activation of ERK and JNK, instead of p38 MAPK pathway. Conclusion: Taken together, these results demonstrated that ALOE is a potential treatment in suppressing LPS-stimulated inflammation reactions targeting NF-κB, JNK and ERK signaling pathways. The anti-inflammatory effects of ALOE indicated that it has the potential to become an effective cosmetic ingredient.