ABSTRACT
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme that promotes the degradation of low-density lipoprotein receptors. It is involved in hyperlipidemia as well as other diseases, such as cancer and skin inflammation. However, the detailed mechanism for PCSK9 on ultraviolet B (UVB)-induced skin lesions was not clear. Thus, the role and possible action mechanism of PCSK9 in UVB-induced skin damage in mice were studied here using siRNA and a small molecule inhibitor (SBC110736) against PCSK9. Immunohistochemical staining revealed a significant increase in PCSK9 expression after UVB exposure, indicating the possible role of PCSK9 in UVB damage. Skin damage, increase in epidermal thickness, and keratinocyte hyperproliferation were significantly alleviated after treatment with SBC110736 or siRNA duplexes, compared with that in the UVB model group. Notably, UVB exposure triggered DNA damage in keratinocytes, whereas substantial interferon regulatory factor 3 (IRF3) activation was observed in macrophages. Pharmacologic inhibition of STING or cGAS knockout significantly reduced UVB-induced damage. In the co-culture system, supernatant from UVB-treated keratinocyte induced IRF3 activation in macrophages. This activation was inhibited with SBC110736 and by PCSK9 knockdown. Collectively, our findings reveal that PCSK9 plays a critical role in the crosstalk between damaged keratinocytes and STING activation in macrophages. The interruption of this crosstalk by PCSK9 inhibition may be a potential therapeutic strategy for UVB-induced skin damage.
Subject(s)
Keratinocytes , Proprotein Convertase 9 , Skin Aging , Skin , Animals , Mice , Keratinocytes/enzymology , Keratinocytes/radiation effects , Macrophages/metabolism , PCSK9 Inhibitors/pharmacology , Proprotein Convertase 9/genetics , Proprotein Convertase 9/metabolism , RNA, Small Interfering/metabolism , Skin/enzymology , Skin/radiation effects , Skin Aging/drug effects , Ultraviolet Rays/adverse effectsABSTRACT
BACKGROUND: In previous studies, the 308-nm light-emitting diode (LED) has been proven safe and effective for treating vitiligo. However, direct comparisons between the 308-nm LED and 308-nm excimer lamp (308-nm MEL) for the treatment of vitiligo are lacking. OBJECTIVE: To compare the efficacy of the 308-nm LED and 308-nm MEL for treating nonsegmental stable vitiligo. PATIENTS AND METHODS: This randomized controlled trial was conducted between January 2018 and August 2023. Enrolled patients were randomly assigned to either the 308-nm LED or the 308-nm MEL groups, both receiving 16 treatment sessions. Adverse events that occurred during the treatment were documented. RESULTS: In total, 269 stable vitiligo patches from 174 patients completed the study. A total of 131 lesions were included in the 308-nm LED group, and 138 lesions were included in the 308-nm MEL group. After 16 treatment sessions, 38.17% of the vitiligo patches in the 308-nm LED group achieved repigmentation of at least 50% versus 38.41% in the 308-nm MEL group. The two devices exhibited similar results in terms of efficacy for a repigmentation of at least 50% (p = .968). The incidence of adverse effects with the two phototherapy devices was comparable (p = .522). CONCLUSIONS: Treatment of vitiligo with the 308-nm LED had a similar efficacy rate to the 308-nm MEL, and the incidence of adverse effects was comparable between the two devices.
Subject(s)
Vitiligo , Humans , Vitiligo/radiotherapy , Vitiligo/therapy , Female , Male , Adult , Middle Aged , Adolescent , Lasers, Excimer/therapeutic use , Lasers, Excimer/adverse effects , Young Adult , ChildABSTRACT
BACKGROUND: Many studies have indicated that negative emotions and personality traits are related to psoriasis, though few have provided causal evidence. METHODS: Our analysis utilized 15 genome-wide association study datasets to identify instrumental variables associated with negative emotions, personality traits and psoriasis vulgaris. Two-sample Mendelian randomization was conducted to identify the causal associations of negative emotions and personality traits with psoriasis vulgaris. To mitigate bias from multiple tests, we adjusted p-values using the Benjamini-Hochberg method. RESULTS: Our study revealed causal links between negative emotions and psoriasis vulgaris, including depressed affect, worry too long, feeling hurt, guilty feelings, mood swings, unenthusiasm, miserableness, fed-up feelings. However, there was no significant evidence of a causal relationship between feeling lonely and psoriasis vulgaris. Additionally, personality traits including neuroticism and openness to experience were found to have causal effects on psoriasis vulgaris. However, no significant evidence supported a causal relationship between agreeableness, conscientiousness, and extraversion with psoriasis vulgaris. CONCLUSION: Our findings suggest that experiencing negative emotions including depressed affect, worrying excessively, feeling hurt, guilty feelings, mood swings, lack of enthusiasm, miserableness and fed-up feelings may pose risks for psoriasis vulgaris. Additionally, neuroticism is associated with a risk of psoriasis vulgaris. Conversely, the openness trait may serve a protective role against psoriasis vulgaris.
Subject(s)
Emotions , Genome-Wide Association Study , Mendelian Randomization Analysis , Personality , Psoriasis , Humans , Psoriasis/psychology , Psoriasis/genetics , Polymorphism, Single NucleotideABSTRACT
BACKGROUND: Psoriasis is a chronic inflammatory dermatosis with an unclear pathogenesis. Mast cells (MCs) can serve as a bridge between innate and adaptive immunity and are involved in the regulation of the inflammatory state and immune homeostasis in diseases. MCs constitutively express interleukin-33 receptor T1/ST2 (IL-33R). IL-33 is a potent MCs activator that is actively secreted by keratinocytes in psoriasis. However, the regulatory role of MCs in psoriasis remains uncertain. Therefore, we hypothesised that IL-33 could promote MC activation to regulate psoriasis development. METHODS: We performed experiments on wild-type (WT) and MC-deficient (Kit Wsh/Wsh) mice, established psoriasis-like mouse models using imiquimod (IMQ), and performed RNA sequencing and transcriptomic analysis of skin lesions. Exogenous administration was performed using recombinant IL-33. Validation and evaluation were performed using PSI scoring, immunofluorescence, immunohistochemistry, and qPCR. RESULTS: We observed an upregulation in the number and activation of MCs in patients with psoriasis and in IMQ-induced psoriasis-like dermatitis. Deficiency of MCs ameliorates IMQ-induced psoriatic dermatitis at an early stage. IL-33 is increased and co-localized with MCs in the dermis of psoriasis-like lesions using immunofluorescence. Compared to WT mice, IMQ-induced KitWsh/Wsh mice demonstrated a delayed response to exogenous IL-33. CONCLUSIONS: MCs are activated by IL-33 in the early stages of psoriasis and exacerbate psoriasis-associated skin inflammation. The regulation of MC homeostasis may be a potential therapeutic strategy for psoriasis. Video Abstract.
Subject(s)
Dermatitis , Psoriasis , Animals , Mice , Dermatitis/pathology , Imiquimod , Interleukin-33/therapeutic use , Mast Cells , Mice, Inbred BALB C , Psoriasis/chemically induced , Psoriasis/drug therapy , Skin/pathologyABSTRACT
BACKGROUND: A light emitting diode (LED), with a wavelength of 308 nm, has been utilized in the dermatologic treatment of vitiligo. OBJECTIVES: We investigated the efficacy and safety of 308-nm LED for use in the treatment of vitiligo. METHODS: We conducted a retrospective study of 70 stable-stage vitiligo patients (with a total of 99 lesions) who received 308-nm LED treatment at the Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College from June 2018 to June 2020. Treatment efficacy was evaluated after 8 treatment sessions, 16 treatment sessions, and the final treatment session, to estimate the percentage of re-pigmentation in the treated area. The Kruskal-Wallis test was used for data analysis. RESULTS: Based on the final treatment session analysis of all 99 lesions, 0 lesions showed no response, 21 lesions showed poor response, 29 lesions showed moderate response, 23 lesions showed good response, and 26 lesions showed excellent response. The efficacy rate was 49.49%, and there was a significant correlation between the six distinct anatomical regions treated and re-pigmentation grade (χ2 = 13.419, p = .009). Among these regions, facial lesions showed the best response to treatment, while the hands and feet lesions showed the poorest response. CONCLUSIONS: The clinical efficacy of 308-nm LED treatment is limited based on the treatment area. It demonstrated significant practical application in the treatment of vitiligo.
Subject(s)
Pigmentation Disorders , Ultraviolet Therapy , Vitiligo , China , Follow-Up Studies , Humans , Retrospective Studies , Treatment Outcome , Vitiligo/radiotherapyABSTRACT
BACKGROUND: Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is a well-known treatment for non-hypertrophic actinic keratoses and superficial basal-cell carcinomas. OBJECTIVES: In this study, we first revealed that ALA-PDT treatment effectively ameliorated the psoriasis-like lesion in imiquimod (IMQ)-induced mouse model and further explored the potential molecular mechanism and related signalling pathways during the treatment. Besides, we also confirmed a significant alleviation of ALA-PDT therapy on IFN-γ-induced over-proliferation of keratinocytes. METHODS: H&E staining was conducted to reveal the histological changes of mice in different groups. The different expression levels of RNA were illustrated by using QRT-PCR. Western blot was performed to confirm the various expression levels of protein in mice. In vitro, cell proliferation and cell cycle were evaluated by cell counting kit-8 and flow cytometry assay, respectively. RESULTS: The result showed that ALA-PDT's anti-proliferation effect and regulation on Socs1/3, JAK1/2 and K17 in IFN-γ-induced keratinocytes were largely weakened by NAC, indicating that ALA-PDT attenuated the proliferation of IFN-γ-induced keratinocytes by enhancing ROS level. CONCLUSIONS: These results demonstrated that ALA-PDT largely activated the productivity of Socs1/3 in a ROS-dependent manner. Socs1/3 is a potential blocker in JAK signalling pathway and inhibits the proliferation and keratinization of keratinocytes in psoriasis.
Subject(s)
Aminolevulinic Acid/pharmacology , Janus Kinases/metabolism , Photochemotherapy , Photosensitizing Agents/pharmacology , Psoriasis/drug therapy , Animals , Drug Evaluation, Preclinical , Female , Imiquimod , Interferon-gamma , Keratinocytes/drug effects , Mice, Inbred BALB C , Psoriasis/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Suppressor of Cytokine Signaling Proteins/metabolismABSTRACT
BACKGROUND: Research on the health effects of exposure to air pollution is growing. However, relatively little attention has been paid to the effects of long-term and cumulative exposure to air pollutants. Individual-level studies on the health consequences of air pollution in China are especially scarce. The purpose of this study is to examine the effect of cumulative exposure to sulfur dioxide (SO2), an air pollutant of particular concern in China, on all-cause mortality in older Chinese adults. METHODS: Using a nationally representative sample of older adults in China (N = 11 199), we tracked mortality over an 11-year period (2000-11). Air pollution data were linked to respondents using provincial identifiers. To examine the effect of cumulative SO2 exposure on mortality, we employed multilevel multinomial logistic regression models that account for within subject clustering of observations over time and clustering at the province level. RESULTS: We found that every 10-µg/m3 increase in cumulative exposure to SO2 increased the odds of death by nearly 1% (OR = 1.008; 95% CI: 1.002-1.014), controlling for province- and individual-level social and economic characteristics. CONCLUSIONS: Our analysis shows that air pollution is a risk factor for morality in older Chinese adults. Findings suggest that stronger SO2 regulations may enhance longevity.
Subject(s)
Air Pollutants/adverse effects , Air Pollution/adverse effects , Mortality , Sulfur Dioxide/adverse effects , Aged , Aged, 80 and over , Air Pollutants/analysis , Air Pollution/analysis , Cause of Death , China/epidemiology , Environmental Monitoring/methods , Female , Humans , Logistic Models , Longitudinal Studies , Male , Risk Factors , Sulfur Dioxide/analysisABSTRACT
Background: Fractional carbon dioxide laser resurfacing (FxCR) is a routine treatment of Dermatology while many patients suffered the damage of skin barrier function after FxCR. Objective: To evaluate the benefits of antimicrobial peptides (AMPs) and hyaluronic acid (HA) compound mask on wound healing after FxCR on human and mouse skin. Methods: Twenty-four subjects were treated with FxCR on the bilateral cheeks. AMPs and HA compound mask was applied on the FxCR-treated area of left cheek. The erythema index (EI), melanin index (MI), transepidermal water loss (TEWL) of FxCR-treated areas on both cheeks were measured. By HE staining, immunohistostaing and western blotting, we analyzed epidermal thickness, FLG, IVL expression and protein levels of cramp in FxCR treated dorsal mice skin. Results: The EI, MI, and TEWL in the AMPs and HA compound mask-treated area of left cheek were significantly lower than those in the untreated area of right cheek. Topically application of AMPs and HA compound mask reduced thickening of mouse skin and also result in an increase in the production of FLG, IVL and cramp. Conclusion: Application of AMPs and HA compound mask is an effective method for enhancing wound healing after FxCR, by reducing transient adverse effects such as erythema, hyperpigmentation, and increased TEWL.
Subject(s)
Anti-Infective Agents/therapeutic use , Cheek , Hyaluronic Acid/therapeutic use , Lasers, Gas/therapeutic use , Plasma Skin Regeneration/methods , Wound Healing/drug effects , Adult , Animals , Carbon Dioxide , Erythema/etiology , Female , Filaggrin Proteins , Humans , Intermediate Filament Proteins/metabolism , Male , Melanins/metabolism , Mice , Water Loss, InsensibleABSTRACT
The aim of this study is to evaluate the efficacy for effectiveness of type A botulinum toxin intradermal injection for facial rejuvenation. Forty female subjects were randomly divided into two groups: BoNTA group and control group. In BoNTA group, each subject's facial skin was treated with intradermal injection of BoNTA, and subjects of the control group were treated with intradermal saline solution injection. Subjects receiving one session of treatment and evaluations were conducted at baseline, four weeks, and twelve weeks after treatment. The outcome assessments included subjective satisfaction scale; blinded clinical assessment; and the biophysical parameters of roughness, elasticity, skin hydration, transepidermal water loss (TEWL), erythema, and melanin index. BoNTA group showed higher physician's global assessment score, subject satisfaction score, roughness, skin hydration, skin elasticity, and lower TEWL compared to that of control group at 12 weeks post-treatment. No significant difference was found among erythema and melanin index at baseline, four, and twelve weeks after treatment among the two major groups. In conclusion, intradermal BoNTA injection can be considered as an effective method for facial rejuvenation.
Subject(s)
Acetylcholine Release Inhibitors/administration & dosage , Botulinum Toxins, Type A/administration & dosage , Cosmetic Techniques , Rejuvenation , Skin Aging , Acetylcholine Release Inhibitors/adverse effects , Adult , Aged , Botulinum Toxins, Type A/adverse effects , China , Cosmetic Techniques/adverse effects , Female , Humans , Injections, Intradermal , Middle Aged , Patient Satisfaction , Photography , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Psoriasis is a chronic, inflammatory skin disease. MicroRNAs (miRNAs) are an abundant class of non-coding RNA molecules. Recent studies have shown that multiple miRNAs are abnormally expressed in patients with psoriasis. The upregulation of miR-374a-5p has been associated with psoriasis severity. However, the specific role of miR-374a-5p in the pathogenesis of psoriasis remain unclear. METHODS: qRT-PCR was employed to validate the expression of miR-374a-5p in psoriatic lesions and in a psoriasis-like cell model constructed using a mixture of M5 (IL-17A, IL-22, OSM, IL-1α, and TNF-α). HaCaT cells were transfected with miR-374a-5p mimic/inhibitor, and assays including EdU, CCK-8, and flow cytometry were conducted to evaluate the effect of miR-374a-5p on cell proliferation. The expression of inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α was verified by qRT-PCR. Bioinformatics analysis and dual-luciferase reporter gene assay were performed to detect the downstream target genes and upstream transcription factors of miR-374a-5p, followed by validation of their expression through qRT-PCR and Western blotting. A psoriasis-like mouse model was established using imiquimod cream topical application. The psoriasis area and severity index scoring, hematoxylin-eosin histology staining, and Ki67 immunohistochemistry were employed to validate the effect of miR-374a-5p on the psoriatic inflammation phenotype after intradermal injection of miR-374a-5p agomir/NC. Additionally, the expression of pathway-related molecules and inflammatory factors such as IL-1ß, IL-17a, and TNF-α was verified by immunohistochemistry. RESULTS: Upregulation of miR-374a-5p was observed in psoriatic lesions and the psoriasis-like cell model. In vitro experiments demonstrated that miR-374a-5p not only promoted the proliferation of HaCaT cells but also upregulated the expression of inflammatory cytokines, including IL-1ß, IL-6, IL-8, and TNF-α. Furthermore, miR-374a-5p promoted skin inflammation and epidermal thickening in the Imiquimod-induced psoriasis-like mouse model. Mechanistic studies revealed that miR-374a-5p led to downregulation of WIF1, thereby activating the Wnt5a/NF-κB signaling pathway. The transcription factor p65 encoded by RELA, as a subunit of NF-κB, further upregulated the expression of miR-374a-5p upon activation. This positive feedback loop promoted keratinocyte proliferation and abnormal inflammation, thereby facilitating the development of psoriasis. CONCLUSION: Our findings elucidate the role of miR-374a-5p upregulation in the pathogenesis of psoriasis through inhibition of WIF1 and activation of the Wnt5a/NF-κB pathway, providing new potential therapeutic targets for psoriasis.
Subject(s)
Adaptor Proteins, Signal Transducing , MicroRNAs , NF-kappa B , Psoriasis , Wnt-5a Protein , Animals , Humans , Mice , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Cell Proliferation , Down-Regulation , HaCaT Cells , Imiquimod , MicroRNAs/metabolism , MicroRNAs/genetics , NF-kappa B/metabolism , Psoriasis/genetics , Psoriasis/pathology , Psoriasis/metabolism , Repressor Proteins/metabolism , Repressor Proteins/genetics , Up-Regulation , Wnt-5a Protein/metabolism , Wnt-5a Protein/geneticsABSTRACT
Exposure to ultraviolet radiation can lead to skin photoaging, which increases the risk of skin tumors. This study aims to investigate how microRNA m6A modification contributes to skin photoaging. This study found that skin fibroblasts exposed to a single UVB dose of 30 mJ/cm2 exhibited characteristics of photoaging. The m6A level of total RNA decreased in photoaged cells with a down-regulated level of METTL14, and overexpression of METTL14 displayed a photoprotective function. Moreover, miR-100-3p was a downstream target of METTL14. And METTL14 could affect pri-miR-100 processing to mature miR-100-3p in an m6A-dependent manner via DGCR8. Furthermore, miR-100-3p targeted at 3' end untranslated region of ERRFI1 mRNA with an inhibitory effect on translation. Additionally, photoprotective effects of overexpression of METTL14 were reversed by miR-100-3p inhibitor or overexpression of ERRFI1. In UVB-induced photoaging of human skin fibroblasts, METTL14-dependent m6A can regulate miR-100-3p maturation via DGCR8 and affect skin fibroblasts photoaging through miR-100-3p/ERRFI1 axis.
Subject(s)
Fibroblasts , Methyltransferases , MicroRNAs , Skin Aging , Ultraviolet Rays , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Fibroblasts/metabolism , Fibroblasts/radiation effects , Methyltransferases/metabolism , Methyltransferases/genetics , Skin Aging/radiation effects , Skin Aging/genetics , Skin/metabolism , Skin/radiation effects , Adenosine/analogs & derivatives , Adenosine/metabolism , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/geneticsABSTRACT
Electrical stimulation therapy is effective in promoting wound healing by rescuing the decreased endogenous electrical field, where self-powered and miniaturized devices such as nanogenerators become the emerging trends. While high-voltage and unidirectional electric field may pose thermal effect and damage to the skin, nanogenerators with lower voltages, pulsed or bidirectional currents, and less invasive electrodes are preferred. Herein, we construct a polydopamine (PDA)-modified poly-L-lactic acid (PLLA) /MXene (PDMP/MXene) nanofibrous composite membrane that generates piezoelectric voltages matching the transepithelial potential (TEP) to accelerate wound healing. PDA coating not only enhances the piezoelectricity of PLLA by dipole attraction and alignment, but also increases its hydrophilicity and facilitates subsequent MXene adhesion for electrical conductivity and stability in physiological environment. When applied as wound dressings in mice, the PDMP/MXene membranes act as a nanogenerators with reduced internal resistances and satisfactory piezoelectric performances that resemble bioelectric potentials (~10 mV) responding to physical activities. The membrane significantly accelerates wound closure by facilitating fibroblast migration, collagen deposition and angiogenesis, and suppressing the expression of inflammatory responses. This piezoelectric fibrous membrane therefore provides a convenient solution for speeding up wound healing by sustained low voltage mimicking bioelectricity, better cell affinity.
ABSTRACT
To investigate whether palmitic acid can be responsible for the induction of inflammatory processes, HaCaT keratinocytes were treated with palmitic acid at pathophysiologically relevant concentrations. Secretion levels of interleukin-6 (IL-6), tumor necrosis factor- α (TNF- α), interleukin-1 ß (IL-1 ß), NF- κ B nuclear translocation, NF- κ B activation, Stat3 phosphorylation, and peroxisome proliferator-activated receptor alpha (PPAR α) mRNA and protein levels, as well as the cell proliferation ability were measured at the end of the treatment and after 24 hours of recovery. Pyrrolidine dithiocarbamate (PDTC, a selective chemical inhibitor of NF- κ B) and goat anti-human IL-6 polyclonal neutralizing antibody were used to inhibit NF- κ B activation and IL-6 production, respectively. Our results showed that palmitic acid induced an upregulation of IL-6, TNF- α , IL-1 ß secretions, accompanied by NF- κ B nuclear translocation and activation. Moreover, the effect of palmitic acid was accompanied by PPAR α activation and Stat3 phosphorylation. Palmitic acid-induced IL-6, TNF- α , IL-1 ß productions were attenuated by NF- κ B inhibitor PDTC. Palmitic acid was administered in amounts able to elicit significant hyperproliferation and can be attenuated by IL-6 blockage. These data demonstrate for the first time that palmitic acid can stimulate IL-6, TNF- α , IL-1 ß productions in HaCaT keratinocytes and cell proliferation, thereby potentially contributing to acne inflammation and pilosebaceous duct hyperkeratinization.
Subject(s)
Interleukin-1beta/biosynthesis , Interleukin-6/biosynthesis , Keratinocytes/metabolism , NF-kappa B/metabolism , Palmitic Acid/pharmacology , Tumor Necrosis Factor-alpha/biosynthesis , Cell Line , Cell Nucleus/metabolism , Cell Proliferation , Cytoplasm/metabolism , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation , Humans , Inflammation , Keratinocytes/cytology , Microscopy, Confocal , Microscopy, Fluorescence , PPAR alpha/metabolism , Phosphorylation , STAT3 Transcription Factor/metabolismABSTRACT
Aim: To identify DNA methylation and transcription biomarkers in the psoriatic epidermis. Materials & methods: Gene transcription and DNA methylation datasets of psoriatic epidermal tissue were obtained from the Gene Expression Omnibus. Machine learning algorithm analysis and weighted gene coexpression network analysis were carried out to screen hub genes. Results: Differentially methylated and expressed genes were identified in the psoriatic epidermis. Six hub genes were selected - GZMB, CRIP1, S100A12, ISG15, CRABP2 and VNN1 - whose transcript levels showed a significant correlation with Psoriasis Area and Severity Index scores and immune infiltration. Conclusion: Psoriatic epidermis is primarily in a hypermethylated status. Epidermis-specific hub differentially methylated and expressed genes are potential biomarkers to help judge the condition of psoriasis.
Subject(s)
DNA Methylation , Psoriasis , Humans , Epidermis/metabolism , Psoriasis/genetics , DNA/metabolism , CpG IslandsABSTRACT
Understanding soil bacterial diversity under nitrogen reduction is necessary for the crucial role in soil nitrogen cycling. However, the effects of combined fertilization on soil chemical properties, microbial community structure, and yield are unknown. This study was conducted to investigate the effect of nitrogen fertilizer reduction with bio-organic fertilizer on soil bacterial community diversity of red raspberry orchard. Six treatments were set in this study: NF-100%, NF-75%, NF-50%, NF-25% and CF, no nitrogen fertilizer and bio-organic fertilizer for CK. The bacterial community structures of soil were analyzed by 16S rRNA gene amplification high-throughput sequencing technology. Nitrogen fertilizer reduction with bio-organic fertilizer increased soil organic matter (SOM), total nitrogen (TN), alkali-hydrolyzable nitrogen (AN), available phosphorus (AP), available potassium (AK), and reduced soil pH. NF-50% and NF-25% treatments increased the yield of red raspberry. Nitrogen reduction combined with bio-organic fertilizer increased the relative abundance of copiotrophic bacteria and decreased the relative abundance of oligotrophic bacteria. The increase in copiotrophic bacteria in the soil of red raspberry orchard could indicate an increase in soil nutrient availability, which have positive implications for soil fertility and production. However, nitrogen fertilizer reduction with bio-organic fertilizer altered the abundance and diversity of soil bacteria, which was reduced compared to CF treatments. The PCoA analysis of the soil bacterial community showed that the community structure of NF-25% treatment was more different from other treatments, indicating that the fertilization method changed the community structure of soil bacteria. The results of a redundancy analysis showed that SOM, pH, AN, TN, and AP were the main factors affecting the microbial community structure. Overall, the reduction of nitrogen fertilizer with bio-organic fertilizer significantly increased the soil nutrient content, reduced the relative abundance and diversity of soil bacteria, increased the relative abundance of beneficial bacteria in the soil, changed the bacterial community structure of soil, increased production and created suitable soil conditions for the red raspberry growth.
Subject(s)
Fertilizers , Rubus , RNA, Ribosomal, 16S/genetics , Alkalies , Bacteria/genetics , Nitrogen , PhosphorusABSTRACT
The long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) plays an oncogenic role in multiple cancers due to its high expression. However, the expression and associated regulatory mechanisms of PVT1 in cutaneous squamous cell carcinoma (cSCC) remain unclear. Our results revealed that PVT1 was highly upregulated in cSCC tissues and cSCC cell lines. To determine the functional role of PVT1 in cSCC, we constructed a stable knockdown cell model of PVT1 in the A431 and COLO16 cell lines using a lentiviral approach. Xenograft tumor experiments of nude mice in vivo, and colony formation, CCK-8, and EdU assays in vitro demonstrated that knockdown of PVT1 could widely suppress cell proliferation in vivo and in vitro. In addition, PVT1 knockdown induced cell cycle arrest and promoted apoptosis, as detected by flow cytometry analysis. Wound healing and transwell assays revealed that PVT1 knockdown significantly inhibited the migration and invasion of CSCC cell lines. To gain insight into the tumorigenic mechanism and explore the potential target molecules of PVT1, we employed label-free quantitative proteomic analysis. The GO, KEGG enrichment, and protein-protein interaction (PPI) networks suggested that 4E-binding protein 1 (4EBP1) is the possible downstream target effector of PVT1, which was validated by western blot analysis. PVT1 silencing markedly decreased 4EBP1 protein expression levels and directly bound 4EBP1 in the cytoplasm of cSCC cells. 4EBP1 overexpression counteracted the effects of PVT1 knockdown on tumorigenesis in cSCC cells, including cell proliferation, apoptosis, migration, and invasion. Our findings provide strong evidence that PVT1 is an oncogene which plays a role in tumorigenesis of cSCC, that PVT1 may interact with 4EBP1 in the cytoplasm as an underlying mechanism in cSCC carcinogenesis, and that PVT1 combined with 4EBP1 may serve as a potential new therapeutic target for cSCC.
ABSTRACT
Browning is a crucial factor affecting the quality of fresh-cut apples. A safe, simple, and effective method to inhibit browning is urgently needed in fresh-cut apple production. We carried out this study to explore the effect mechanism of exogenous selenium (Se) fertilizer on fresh-cut apple browning. During the development of apples, 0.75 kg/plant Se fertilizer was exerted on the 'Fuji' apple tree at the critical stage of the young fruit stage (late May), early fruit expansion stage (late June), and fruit expansion stage (late July), an equal amount of Se-free organic fertilizer was used as control. Polyphenol oxidase (PPO), peroxidase (POD), and phenylalanine ammonia-lyase (PAL) activities, phenolic and malondialdehyde (MDA) content, antioxidant enzymes activity, and DPPH free radical scavenging rate of the apple at different development stages were investigated. The highest Se accumulation efficiency was observed in apple fruit one month after applying Se fertilizer, which was 41.1%. Se-rich apples exhibited a more remarkable ability to resist browning than control after fresh-cut. The anti-browning effect of the fertilization group (M7) was the best, the PPO activity decreased to 0.5 × 103 U kg-1, and the browning index was 28.6. The total Se content (TSC) of 331.4 µg kg-1 DW and organic Se content (OSC) of 292.0 µg kg-1 DW were the highest in the apple samples, reached the classification standard of Se content in Se-rich food. The correlation analysis found that fresh-cut apple browning was closely related to antioxidant capacity and PPO activity. The stronger the antioxidant capacity of fresh-cut apples treated with Se fertilizer, the lower their browning degree. Therefore, exogenous Se can alleviate fresh-cut apples browning by improving antioxidant capacity and reducing PPO activity. Se-rich apples could increase the Se content of the human essential trace element and inhibit the browning of fresh-cut apples, which would become a new, safe and effective way to solve the fresh-cut apples browning.
Subject(s)
Malus , Selenium , Humans , Antioxidants/pharmacology , Fruit/chemistry , Selenium/pharmacology , Fertilizers/analysis , Catechol OxidaseABSTRACT
Psoriasis is a chronic inflammatory immune skin disease mediated by genetic and environmental factors. As a bridge between innate and adaptive immunity, mast cells are involved in the initiation, development, and maintenance of psoriasis by interactions and communication with a variety of cells. The current review describes interactions of mast cells with T cells, Tregs, keratinocytes, adipocytes, and sensory neurons in psoriasis to emphasize the important role of mast cell-centered cell networks in psoriasis.
Subject(s)
Mast Cells , Psoriasis , Humans , Adaptive Immunity , Skin , KeratinocytesABSTRACT
ObjectivesThis study aims to examine the relationship between psychological well-being (PWB) and cognitive function in older adults in China. Methods: Data are from the Chinese Longitudinal Healthy Longevity Survey. Analyses were restricted to 9,487 older persons (age ≥ 60) without cognitive impairment at baseline. Respondents were followed over a 12-year period. Cognitive function was assessed using the Chinese version of the Mini-Mental State Examination (C-MMSE). PWB was assessed using a composite index capturing optimism, conscientiousness, neuroticism, loneliness, personal control, self-esteem, and happiness. Results: Multilevel mixed effects generalized linear models showed that respondents with greater PWB had a slower rate of cognitive decline over time, adjusting for sociodemographic and health characteristics. In addition, multilevel multinomial logistic regression models showed that greater PWB was associated with lower odds of developing cognitive impairment. Conclusions: Findings suggest that fostering PWB may prevent or delay adverse cognitive changes.