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BACKGROUND: The survival of critically ill patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT) is highly dependent on their nutritional status. OBJECTIVES: The prognostic nutritional index (PNI) is an indicator used to assess nutritional status and is calculated as: PNI = (serum albumin in g/dL) × 10 + (total lymphocyte count in/mm3) × 0.005. In this retrospective study, we investigated the correlation between this index and clinical outcomes in critically ill patients with AKI receiving CRRT. METHODS: We analyzed data from 2076 critically ill patients admitted to the intensive care unit at Changhua Christian Hospital, a tertiary hospital in central Taiwan, between January 1, 2010, and April 30, 2021. All these patients met the inclusion criteria of the study. The relationship between PNI and renal replacement therapy-free survival (RRTFS) and mortality was examined using logistic regression models, Cox proportional hazard models, and propensity score matching. High utilization rate of parenteral nutrition (PN) was observed in our study. Subgroup analysis was performed to explore the interaction effect between PNI and PN on mortality. RESULTS: Patients with higher PNI levels exhibited a greater likelihood of achieving RRTFS, with an adjusted odds ratio of 2.43 (95% confidence interval [CI]: 1.98-2.97, p-value < 0.001). Additionally, these patients demonstrated higher survival rates, with an adjusted hazard ratio of 0.84 (95% CI: 0.72-0.98) for 28-day mortality and 0.80 (95% CI: 0.69-0.92) for 90-day mortality (all p-values < 0.05), compared to those in the low PNI group. While a high utilization rate of parenteral nutrition (PN) was observed, with 78.86% of CRRT patients receiving PN, subgroup analysis showed that high PNI had an independent protective effect on mortality outcomes in AKI patients receiving CRRT, regardless of their PN status. CONCLUSIONS: PNI can serve as an easy, simple, and efficient measure of lymphocytes and albumin levels to predict RRTFS and mortality in AKI patients with require CRRT.
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Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Estado Terminal , Avaliação Nutricional , Estado Nutricional , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Injúria Renal Aguda/terapia , Injúria Renal Aguda/mortalidade , Taiwan/epidemiologia , Prognóstico , Estado Terminal/mortalidade , Estado Terminal/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Nutrição Parenteral/estatística & dados numéricosRESUMO
BACKGROUND: Identifying new targets in triple negative breast cancer (TNBC) remains critical. REG3A (regenerating islet-derived protein 3 A), a calcium-dependent lectin protein, was thoroughly investigated for its expression and functions in breast cancer. METHODS: Bioinformatics and local tissue analyses were employed to identify REG3A expression in breast cancer. Genetic techniques were employed to modify REG3A expression, and the resulting effects on the behaviors of breast cancer cells were examined. Subcutaneous xenograft models were established to investigate the involvement of REG3A in the in vivo growth of breast cancer cells. RESULTS: Analysis of the TCGA database uncovered increased REG3A levels in human breast cancer tissues. Additionally, REG3A mRNA and protein levels were elevated in TNBC tissues of locally treated patients, contrasting with low expression in adjacent normal tissues. In primary human TNBC cells REG3A shRNA notably hindered cell proliferation, migration, and invasion while triggering caspase-mediated apoptosis. Similarly, employing CRISPR-sgRNA for REG3A knockout showed significant anti-TNBC cell activity. Conversely, REG3A overexpression bolstered cell proliferation and migration. REG3A proved crucial for activating the Akt-mTOR cascade, as evidenced by decreased Akt-S6K1 phosphorylation upon REG3A silencing or knockout, which was reversed by REG3A overexpression. A constitutively active mutant S473D Akt1 (caAkt1) restored Akt-mTOR activation and counteracted the proliferation inhibition and apoptosis induced by REG3A knockdown in breast cancer cells. Crucially, REG3A played a key role in maintaining mTOR complex integrity. Bioinformatics identified zinc finger protein 680 (ZNF680) as a potential REG3A transcription factor. Knocking down or knocking out ZNF680 reduced REG3A expression, while its overexpression increased it in primary breast cancer cells. Additionally, enhanced binding between ZNF680 protein and the REG3A promoter was observed in breast cancer tissues and cells. In vivo, REG3A shRNA significantly inhibited primary TNBC cell xenograft growth. In REG3A-silenced xenograft tissues, reduced REG3A levels, Akt-mTOR inhibition, and activated apoptosis were evident. CONCLUSION: ZNF680-caused REG3A overexpression drives tumorigenesis in breast cancer possibly by stimulating Akt-mTOR activation, emerging as a promising and innovative cancer target.
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Apoptose , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas Associadas a Pancreatite , Proteínas Proto-Oncogênicas c-akt , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Feminino , Proteínas Associadas a Pancreatite/metabolismo , Proteínas Associadas a Pancreatite/genética , Animais , Camundongos , Linhagem Celular Tumoral , Apoptose/genética , Movimento Celular/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Carcinogênese/genética , Transdução de Sinais , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
SET domain bifurcated 1 (SETDB1), a pivotal histone lysine methyltransferase, is transported to the cytoplasm via a chromosome region maintenance 1 (CMR1)dependent pathway, contributing to nonhistone methylation. However, the function and underlying mechanism of cytoplasmic SETDB1 in breast cancer remain elusive. In the present study, immunohistochemistry revealed that elevated cytoplasmic SETDB1 was correlated with lymph node metastasis and more aggressive breast cancer subtypes. Functionally, wound healing and Transwell assays showed that cytoplasmic SETDB1 is key for cell migration and invasion, as well as induction of epithelialmesenchymal transition (EMT), which was reversed by leptomycin B (LMB, a CMR1 inhibitor) treatment. Furthermore, RNAseq and metabolite detection revealed that cytoplasmic SETDB1 was associated with metabolism pathway and elevated levels of metabolites involved in the Warburg effect, including glucose, pyruvate, lactate and ATP. Immunoblotting and reverse transcriptionquantitative PCR verified that elevation of cytoplasmic SETDB1 contributed to elevation of cMYC expression and subsequent upregulation of lactate dehydrogenase A (LDHA) expression. Notably, gain and lossoffunction approaches revealed that LDHA overexpression in T47D cells enhanced migration and invasion by inducing EMT, while its depletion in SETDB1overexpressing MCF7 cells reversed SETDB1induced migration and invasion, as well as the Warburg effect and EMT. In conclusion, subcellular localization of cytoplasmic SETDB1 may be a pivotal factor in breast cancer progression. The present study offers valuable insight into the novel functions and mechanisms of cytoplasmic SETDB1.
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Neoplasias da Mama , Domínios PR-SET , Feminino , Humanos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Citoplasma/metabolismo , Regulação Neoplásica da Expressão Gênica , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Lactato Desidrogenase 5/genética , Lactato Desidrogenase 5/metabolismoRESUMO
The chemical constituents of Schizonepetae Spica were qualitatively analyzed by UHPLC-Q-TOF-MS/MS. An Agilent poroshell 120 SB-C_(18) column(3.0 mm×100 mm, 2.7 µm) was used for gradient elution with 0.1% formic acid water(A)-acetonitrile(B) solution as mobile phase at the flow rate of 0.4 mL·min~(-1) and column temperature of 45 â. The data were collected by scanning in positive and negative ion modes, and the compounds were identified by comparison of reference materials and PeakView software. Ninety-seven compounds were identified from Schizonepetae Spica, including 28 flavonoids, 23 phenolic acids, 23 fatty acids, 15 terpenoids, and 8 other compounds. The UHPLC-Q-TOF-MS/MS method established in this study can identify the chemical components of Schizonepetae Spica rapidly, accurately, and comprehensively, and provide a basis for the basic study of pharmacodynamic substances of Schizonepetae Spica.
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Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Flavonoides/análise , TerpenosRESUMO
Acne vulgaris, one of the most common skin diseases, is a chronic cutaneous inflammation of the upper pilosebaceous unit (PSU) with complex pathogenesis. Inflammation plays a central role in the pathogenesis of acne vulgaris. During the inflammatory process, the innate and adaptive immune systems are coordinately activated to induce immune responses. Understanding the infiltration and cytokine secretion of differential cells in acne lesions, especially in the early stages of inflammation, will provide an insight into the pathogenesis of acne. The purpose of this review is to synthesize the association of different cell types with inflammation in early acne vulgaris and provide a comprehensive understanding of skin inflammation and immune responses.
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Acne Vulgar , Dermatite , Dermatopatias , Humanos , Acne Vulgar/etiologia , Pele , Inflamação/patologia , Dermatopatias/complicações , Expressão Gênica , Dermatite/complicaçõesRESUMO
BACKGROUND: Heart failure (HF), a common cardiovascular condition, is characterized by significant morbidity and mortality. While traditional Chinese medicine (TCM) is often used as a complementary approach in HF management, systematic evaluations of its impact on clinical outcomes, TCM syndrome scores, and B-type natriuretic peptide (BNP) levels are lacking. This study fills this gap through a comprehensive analysis of randomized controlled trials (RCTs) focusing on TCM for HF treatment. It encompasses an assessment of methodological quality, a meta-analysis, and an evaluation of evidence quality based on established standards. The results offer crucial insights into the potential advantages and constraints of TCM in HF management. AIM: To systematically analyze the effects of TCM on the clinical comprehensive outcomes, TCM syndrome scores, and BNP levels in patients with HF and evaluated the quality of evidence for these trials. METHODS: RCTs on TCM for HF treatment published since the establishment of the database were searched in four Chinese and English databases, including China National Knowledge Infrastructure, Wanfang, VIP Information Chinese Science and Technology Journal, and PubMed. Methodological quality was assessed for the included studies with the Cochrane risk-of-bias assessment tool, and the meta-analysis and publication bias assessment was performed with the RevMan5.3 software. Finally, the quality of evidence was rated according to the GRADE criteria. RESULTS: A total of 1098 RCTs were initially retrieved. After screening, 16 RCTs were finally included in our study, which were published between 2020 and 2023. These RCTs involved 1660 HF patients, including 832 in the TCM group [TCM combined with conventional Western medicine (CMW) treatment] and 828 in the CWM group (CWM treatment). The course of treatments varied from 1 wk to 3 months. TCM syndrome differentiation was analyzed in 11 of the included RCTs. In all included RCTs, outcome indicators included comprehensive clinical outcomes, TCM syndrome scores, and BNP levels. The meta-analysis results showed significant differences between the TCM and CWM groups in terms of comprehensive clinical outcomes [risk ratio = -0.54; 95% confidence interval (CI) = -0.61, -0.47; P < 0.00001], TCM syndrome scores [weighted mean difference (WMD) = -142.07; 95%CI = -147.56, -136.57; P < 0.00001], and BNP levels (WMD = -142.07; 95%CI = -147.56, -136.57; P < 0.00001). According to the GRADE criteria, RCTs where "TCM improves clinical comprehensive outcomes" were rated as low-quality evidence, and RCTs where "TCM reduces TCM syndrome scores" or "TCM decreases BNP levels" were rated as medium-quality evidence. CONCLUSION: TCM combined with CWM treatment effectively improves comprehensive clinical outcomes and diminishes TCM syndrome scores and BNP levels in HF patients. Given the low and medium quality of the included RCTs, the application of these results should be cautious.
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Autism spectrum disorder (ASD) is a common neurological disorder. Although the etiologies of ASD have been widely speculated, evidence also supports the pathogenic role of cutaneous inflammation in autism. The prevalence of ASD is higher in individuals with inflammatory dermatoses than in those without inflammatory diseases. Anti-inflammation therapy alleviates symptoms of ASD. Recent studies suggest a link between epidermal dysfunction and ASD. In the murine model, mice with ASD display epidermal dysfunction, accompanied by increased expression levels of proinflammatory cytokines in both the skin and the brain. Children with ASD, which develops in their early lifetime, also exhibit altered epidermal function. Interestingly, improvement in epidermal function alleviates some symptoms of ASD. This line of evidence suggests a pathogenic role of cutaneous dysfunction in ASD. Either an improvement in epidermal function or effective treatment of inflammatory dermatoses can be an alternative approach to the management of ASD. We summarize here the current evidence of the association between the skin and ASD.
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To address the adjustment of the Chinese agricultural industry and to better promote the development of Chinese household biogas, this article summarizes and analyzes the spatial distribution characteristics and influencing factors of the type and number of biogas digesters, biogas production, biogas fermentation materials, and methods of fermentation residue utilization and ecological agriculture with household biogas by compiling a dataset covering 31 provincial administrative regions in China. The results show that hydraulic biogas digesters are distributed mainly in northwestern and northeastern China; in addition, continuously stirred biogas digesters and bottom-discharging biogas digesters are distributed mainly in southern and northern China, respectively. Because of temperature and population, the Sichuan and Henan Provinces have the highest number of biogas digesters and biogas production. The type of biogas fermentation materials depends on the local raw materials. Biogas slurry and residue are widely used as fertilizers; furthermore, biogas slurry is used for seed soaking in northeastern and southern China, and biogas residue is used as feed in central southern and northern China. The "Three-in-one" and "Four-in-one" biogas ecological models are used mostly in southern and northern China, respectively, and both are mainly affected by temperature. Finally, we propose various problems and countermeasures to enhance the development of the household biogas industry in China. Our findings are critical for China's policymakers to adopt effective measures for promoting the development of cleaner energy and the layout of the agricultural industry.
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Biocombustíveis , Características da Família , Biocombustíveis/análise , China , Fermentação , Agricultura/métodosRESUMO
Hiptagestenopterum K.Tan & M.X.Ren, a new species of Hiptage collected from a deep valley close to the Nujiang Gorge, northwest of Yunnan Province, China, is described and illustrated based on molecular and morphological data. The new species was found isolated in an entrenched valley of the Laowo River, a tributary of the Nujiang River, at the northern edge of the distribution range of the genus. H.stenopterum shares some morphological similarities with the narrowly endemic H.incurvatum and H.lushuiensis. However, H.stenopterum is easily distinguished by its oblanceolate lateral wing of winged mericarp, 10 to 12 calyx glands, and branchlets densely rusty tomentose. The new species status is also supported by molecular phylogenetic analyses based on nuclear ribosome internal transcribed spacer (nrITS), which showed distinct systematic boundaries from the most morphologically similar species, H.incurvatum and their morphological relatives, H.lushuiensis.
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BACKGROUND: Obesity is a condition defined by an excess amount of body fat, with body mass index (BMI) of 30 and higher. It is associated with a number of other medical conditions, including insulin resistance, diabetes mellitus, and cardiovascular diseases, as well as dyslipidemia, and it is also associated with several cutaneous disorders such as atopic dermatitis, psoriasis, intertriginous dermatitis, acanthosis nigricans and skin infections. SUMMARY: Evidence suggests a link between obesity and epidermal dysfunction. Generally, individuals with obesity display higher transepidermal water loss rate and lower stratum corneum hydration levels, although no association of obesity with epidermal dysfunction has been documented. Results of skin surface pH are controversial. But study demonstrated a positive correlation of BMI with skin surface pH on both the forearm and the shin in males, suggesting that the changes in epidermal function vary with gender in individuals with obesity. KEY MESSAGES: This review summarizes the association between obesity and epidermal function, and discusses possible underlying mechanisms. Individuals with obesity exhibit poor epidermal permeability barrier and lower stratum corneum hydration levels. Because of the pathogenic role of compromised epidermal function in inflammation, which is also linked to obesity, improvement in epidermal function could benefit individuals with obesity, particularly those with abnormalities in epidermal function.
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Dermatite Atópica , Dermatopatias , Masculino , Humanos , Epiderme/metabolismo , Pele/patologia , Dermatopatias/patologia , Administração Cutânea , Dermatite Atópica/metabolismo , Perda Insensível de ÁguaRESUMO
Two serious health conditions, obesity and atopic dermatitis (AD), share some pathological features such as insulin resistance, leptin resistance and inflammation, and a growing body of evidence suggests a link between obesity and AD. Obesity predisposes an individual to and/or worsens AD, whereas AD increases the risk of obesity. Obesity and AD's interactions are mediated by cytokines, chemokines and immune cells. Obese individuals with AD are more resistant to anti-inflammatory therapy, while weight loss can alleviate AD. In this review, we summarize the evidence linking AD and obesity. We also discuss the pathogenic role of obesity in AD, and vice versa. Because of the connection between these two conditions, mitigation of one could possibly prevent the development of or alleviate the other condition. Effective management of AD and weight loss can enhance the wellness of individuals with both of these conditions. However, proper clinical studies are warranted to validate this speculation.
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Dermatite Atópica , Humanos , Obesidade/complicações , Inflamação/complicaçõesRESUMO
Qishen Gubiao granules, a traditional Chinese medicine preparation composed of nine herbs, have been widely used to prevent and treat coronavirus disease 2019 with good clinical efficacy. In the present study, an integrated strategy based on chemical profiling followed by network pharmacology and molecular docking was employed, to explore the active components and potential molecular mechanisms of Qishen Gubiao granules in the therapy of coronavirus disease 2019. Using the ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technique, a total of 186 ingredients corresponding to eight structure types in Qishen Gubiao preparation were identified or structurally annotated with the elucidation of the fragmentation pathways in the typical compounds. The network pharmacology analysis screened 28 key compounds including quercetin, apigenin, scutellarein, luteolin and naringenin acting on 31 key targets, which possibly modulated signal pathways associated with immune and inflammatory responses in the treatment of coronavirus disease 2019. The molecular docking results observed that the top 5 core compounds had a high affinity for angiotensin-converting enzyme 2 and 3-chymotrypsin-like protease. This study proposed a reliable and feasible approach for elucidating the multi-components, multi-targets, and multi-pathways intervention mechanism of Qishen Gubiao granules against coronavirus disease 2019, providing a scientific basis for its further quality evaluation and clinical application.
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COVID-19 , Medicamentos de Ervas Chinesas , Humanos , Cromatografia Líquida de Alta Pressão , Simulação de Acoplamento Molecular , Farmacologia em Rede , Medicina Tradicional Chinesa , Espectrometria de MassasRESUMO
This study used both the element occurrence form analysis and the chronic health risk assessment method to investigate the accumulation characteristics of heavy metals in the soil-crop system and the health risk assessment of agricultural products in northeastern Yunnan, which is a typical area of Southwest China where heavy metals are enriched in soil. Based on the study of 1137 groups of agricultural products and corresponding root soils, the results showed that the soil cadmium (Cd) and lead (Pb) in the lead-zinc ore concentration area were higher than the risk-intervention values of the "Soil Environmental Quality Risk control standard for soil contamination of agricultural land" (GB 15618-2018), whereas the soil Cd in the other parent material areas was within the screening-intervention buffer zone, and Pb was below the minimum risk-screening value. According to the National Food Safety Standard of China (GB 2762-2017), the heavy metal Cd in potatoes and soybeans in the area seriously exceeded the standard, the heavy metal Pb in tartary buckwheat and walnut exceeded the limit value, and the exceeding rate of heavy metal Cd in crops from these parent material areas showed: clastic rock>basalt>lead-zinc ore>carbonate ≈ Quaternary sedimentary>sand (mud) rock. According to the U.S. Environmental Protection Agency's assessment method for the chronic health risk of heavy metal intake by humans, the grains and potatoes, staple foods, and fruits had low chronic health risks of heavy metal intake. Agricultural products from the parent material area of clastic rock, sand (mud) rock, Quaternary sedimentary, and lead-zinc ore concentration showed health risks; with the change in soil physical and chemical properties and the increase in the types of edible crops, the risk will gradually increase. Based on this research, it is urgent to carry out real-time monitoring of agricultural products in the area.
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Metais Pesados , Poluentes do Solo , Humanos , Solo/química , Cádmio/análise , Areia , Chumbo/análise , China , Poluentes do Solo/análise , Metais Pesados/análise , Zinco , Medição de Risco , Produtos Agrícolas/química , Monitoramento AmbientalRESUMO
Ammonia (NH3) volatilization is a major pathway of soil nitrogen loss in tropical farmland, causing many environmental issues. Biochar can improve soil quality and affect soil NH3 volatilization. However, little is known about the effects of tropical crop residue biochar on soil NH3 volatilization in tropical farmland. Therefore, a laboratory incubation study was conducted using four kinds of tropical crop residue biochar (pineapple straw (stem and leaves), banana straw, cassava straw and sugarcane bagasse pyrolyzed at 500 °C) with five addition rates (0.5%, 1%, 2%, 4%, and 6%) to evaluate their impact on NH3 volatilization from tropical latosols. The results showed that NH3 volatilization peaked twice under biochar application, once at 1-5 days and again at 12-16 days. The cumulative NH3 volatilization (0.14-0.47 mg kg-1) of the 20 biochar treatments was higher than that of the control (0.12 mg kg-1). With the increase in the biochar addition rate, the soil pH, soil organic matter (SOM), urease activity, nitrate nitrogen content (NO3--N), nitrification rate and cumulative NH3 volatilization increased gradually, and the 6% biochar treatment resulted in the highest NH3 volatilization loss (0.19-0.47 mg kg-1). The type of biochar is also a main factor affecting soil NH3 volatilization. The cumulative NH3 volatilization was the highest under pineapple straw biochar, as it was 19-43% higher than when the other three biochars were applied. However, sugarcane bagasse biochar had the lowest cumulative NH3 volatilization due to its low quartz, sylvite and calcite contents, lack of -OH hydroxyl groups and high adsorbability. NH3 volatilization was positively correlated with the soil pH, SOM, urease activity, NO3--N and nitrification rate. In conclusion, four tropical crop residue biochars can increase NH3 volatilization in tropical latosols, so reducing NH3 volatilization needs to be further considered in tropical crop residue biochar applications.
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Ananas , Manihot , Musa , Oryza , Saccharum , Amônia/análise , Celulose , Carvão Vegetal , Fazendas , Fertilizantes/análise , Nitrogênio/análise , Solo/química , VolatilizaçãoRESUMO
Acne vulgaris (AV) is a chronic skin disease involving inflammation of the pilosebaceous units. Propionibacterium acnes (P. acnes) hypercolonization is one pathogenic factor for AV. P. acnes that triggers interleukin-1ß (IL-1ß) by activating the pyrin domain-containing 3 protein (NLRP3) inflammasome of the NOD-like receptor family in human monocytes. Reactive oxygen species (ROS) acts as a trigger for the production of IL-8 and activates theNLRP3 inflammasome. IL-8 promotes the metastasis and multiplication of different cancerous cells, whereas keratinocyte proliferation and migration contribute to the progression of AV. A steroidal saponin called polyphyllin I (PPI) that is extracted from Paris polyphylla's rhizomes has anti-inflammatory properties. This study investigates the regulatory role of P. acnes in the secretion of IL-8 mediated by the CD36/NADPH oxidase 1 (NOX1)/ROS/NLRP3/IL-1ß pathway and the effects of PPI on the CD36/NOX1/ROS/NLRP3/IL-1ß/IL-8 pathway and human keratinocyte proliferation and migration. HaCaT cells were cultured and stimulated with 108 CFU/ml of P. acnes for 0, 6, 12, 18, 24, 30, and 36 hours. P. acnes induced IL-8 secretion from HaCaT cells via the CD36/NOX1/ROS/NLRP3/IL-1ß pathway. PPI inhibited the CD36/NLRP3/NOX1/ROS/IL-8/IL-1ß pathway and HaCaT cell proliferation and migration. PPI alleviates P. acnes-induced inflammatory responses and human keratinocyte proliferation and migration, implying a novel potential therapy for AV.
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Acne vulgaris (AV) is a chronic inflammatory disease of the pilosebaceous unit, and Propionibacterium acnes (P. acnes) has been implicated in acne inflammation. Numerous studies have shown that non-coding RNAs play important roles in regulating the pathophysiological processes of acne. In addition, the first imprinted long non-coding RNA (lncRNA) identified, H19, plays a critical role in inflammatory disease. However, the expression and role of H19 in AV remain unclear. In this study, we investigated the effects of H19 in keratinocytes and explored the regulatory mechanisms underlying these effects. H19 was upregulated in keratinocytes treated with P. acnes in a concentration-dependent manner. The phosphorylated forms of the nuclear factor (NF)-κB-related proteins IκBα (p-IκBα) and p65 (p-P65) were significantly upregulated after P. acnes treatment. Additionally, secretion of the proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 was upregulated in a concentration-dependent manner. Knockdown of H19 inhibited the expression of p-IκBα and p-P65 as well as the secretion of TNF-α, IL-6, and IL-8 in keratinocytes treated with P. acnes. Moreover, H19 was found to exert its proinflammatory effects by activating NF-κB. H19, which was localized mainly in the cytoplasm of keratinocytes, facilitated Toll-like receptor 2 (TLR2) expression by acting as a miR-196a sponge. H19 thus promoted the activation of NF-κB and the secretion of inflammatory cytokines through the miR-196a/TLR2 axis. These findings provide novel insight into the pathogenesis of AV.
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Acne Vulgar/metabolismo , MicroRNAs/biossíntese , NF-kappa B/biossíntese , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/biossíntese , Receptor 2 Toll-Like/biossíntese , Acne Vulgar/patologia , Acne Vulgar/prevenção & controle , Técnicas de Silenciamento de Genes/métodos , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologiaAssuntos
Bacteriemia/patologia , Chryseobacterium/patogenicidade , Úlcera da Córnea/patologia , Infecções por Flavobacteriaceae/patologia , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Bacteriemia/cirurgia , Chryseobacterium/efeitos dos fármacos , Chryseobacterium/enzimologia , Chryseobacterium/crescimento & desenvolvimento , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/microbiologia , Túnica Conjuntiva/patologia , Túnica Conjuntiva/cirurgia , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/microbiologia , Úlcera da Córnea/cirurgia , Farmacorresistência Bacteriana Múltipla , Feminino , Infecções por Flavobacteriaceae/diagnóstico , Infecções por Flavobacteriaceae/microbiologia , Infecções por Flavobacteriaceae/cirurgia , Humanos , Retalhos Cirúrgicos/microbiologia , Retalhos Cirúrgicos/patologia , Falha de Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoRESUMO
The Cutibacterium acnes (also called Propionibacterium acnes, P. acnes)-induced proliferation and migration of keratinocytes contribute to acne vulgaris (AV), which is a common inflammatory skin disease that causes physical and psychological impairments. Piceatannol (3, 5, 3', 4'-tetrahydroxy-trans-stilbene, PCT) is naturally present in many human diets and plays antioxidant and anti-inflammatory roles that inhibit cell proliferation and migration. We aimed to analyse the functions and underlying mechanisms of PCT in P. acnes-stimulated keratinocytes. First, PCT showed no toxicity against the normal human keratinocyte cell line HaCaT but inhibited P. acnes-induced HaCaT cell proliferation. Next, PCT promoted the nuclear translocation and target gene transcription of the antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), thereafter decreasing intracellular reactive oxygen species (ROS) levels. In addition, PCT inhibited the nuclear translocation of p65 [a subunit of nuclear factor kappa B (NF-κB)] and the secretion of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and interleukin-8 (IL-8). Finally, a transfection assay showed that PCT inhibited P. acnes-induced HaCaT cell proliferation and migration by activating the antioxidant Nrf2 pathway and inhibiting the inflammatory NF-κB pathway. Our data suggested that PCT alleviated P. acnes-induced HaCaT cell proliferation and migration through its antioxidant and anti-inflammatory roles, suggesting the potential of PCT to treat AV.
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Acne Vulgar/prevenção & controle , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Queratinócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pele/efeitos dos fármacos , Estilbenos/farmacologia , Acne Vulgar/metabolismo , Acne Vulgar/microbiologia , Acne Vulgar/patologia , Linhagem Celular , Interações Hospedeiro-Patógeno , Humanos , Queratinócitos/metabolismo , Queratinócitos/microbiologia , Queratinócitos/patologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Propionibacterium acnes/patogenicidade , Transdução de Sinais , Pele/metabolismo , Pele/microbiologia , Pele/patologia , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismoRESUMO
Breast cancer is one of the leading fatal diseases for women worldwide who cannot have surgery typically have to rely on systemic chemotherapy to extend their survival. Doxorubicin (DOX) is one of the most commonly used chemotherapeutic agents against breast cancer, but acquired resistance to DOX can seriously impede the efficacy of chemotherapy, leading to poor prognosis and recurrences of cancer. Resveratrol (RES) is a phytoalexin with pharmacological antitumor properties, but its underlying mechanisms are not clearly understood in the treatment of DOX-resistant breast cancer. We used cell viability assays, cell scratch tests, and transwell assays combined with Western blotting and immunofluorescent staining to evaluate the effects of RES on chemoresistance and the epithelial-mesenchymal transitions (EMTs) in adriamycin-resistant MCF7/ADR breast cancer cells, and to investigate its underlying mechanisms. The results showed that a treatment of RES combining with DOX effectively inhibited cell growth, suppressed cell migration, and promoted cell apoptosis. RES reversed EMT properties of MCF7/ADR cells by modulating the connection between SIRT1 and ß-catenin, which provides a hopeful therapeutic avenue to conquer DOX-resistance and thereby prolong survival rates in breast cancer patients.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Doxorrubicina/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Resveratrol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , beta Catenina/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Expressão Gênica , Humanos , Sirtuína 1/genética , beta Catenina/genéticaRESUMO
Propionibacterium acnes (P. acnes) has been implicated in the progression of acne inflammation. Because current acne medications have various side effects, it is necessary to explore alternative medications possessing anti-inflammatory activity against P. acnes. We investigated the inhibitory effects of polyphyllin I (PPI) on P. acnes-induced inflammation in vitro. In this study, we examined the effects of PPI on the production of inflammatory cytokines in HaCaT keratinocytes treated with heat-killed P. acnes. These treated HaCaT keratinocytes showed increased expression of Toll-like receptor 2 (TLR2) and production of inflammatory cytokines. PPI significantly suppressed the secretion of inflammatory cytokines, including interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α, and the expression of TLR2 in P. acnes-treated cells. Moreover, we studied the influence of PPI on the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in P. acnes-treated keratinocytes. PPI diminished the activation of NF-κB. Phosphorylated p38 levels were markedly increased after treatment with heat-killed P. acnes but were decreased after treatment with PPI, while the effect of PPI on ERK phosphorylation was not significant. Heat-killed P. acnes and PPI did not have any effect on JNK phosphorylation. Furthermore, we confirmed that NF-κB p65 inhibitor (BAY11-7082), p38 MAPK inhibitor (SB203580), and PPI blocked the expression of IL-8 in heat-killed P. acnes-treated cells. These results demonstrated that PPI has potential for development as a treatment for acne inflammation.