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BACKGROUND: To date, multiple cases of adverse reactions to COVID-19 vaccines have been reported worldwide. Alopecia areata (AA) is an uncommon type of adverse reaction reported in some articles and has a significant social and psychological impact on patients. Our study aimed to review the AA and COVID-19 vaccine literature. METHODS: This systematic review was conducted by searching for articles on AA following COVID-19 vaccines in international databases such as Embase, MEDLINE, PubMed, Web of Knowledge, and Ovid from December 2019 to December 30, 2023. We included studies that provided data for AA patients following COVID-19 vaccination with at least one dose. Data on sex, age, country/region of origin, vaccine type, days between vaccination and symptom presentation, manifestations of AA, trichoscopy and histopathological findings, treatment, and outcomes were included. RESULTS: In total, 579 explored studies were identified and assessed, and 25 articles with a total of 51 patients were included in the review. Twenty-seven (52.9%) patients developed new-onset AA following receiving the COVID-19 vaccine, and AA recurrence or exacerbation occurred after receiving the COVID-19 vaccine in 24 (47.1%) patients with preexisting disease. Five vaccines were reported to cause AA in all cases. The Pfizer vaccine (45.1%) was the most frequently reported, followed by the ChAdOx1 nCoV-19 vaccine (27.5%), Moderna mRNA-1273 (19.6%), Sinopharm (3.9%) and SinoVac (3.9%). AA occurred most frequently within one month after the 1st dose, and then, the incidence decreased gradually with time. Topical or systemic corticosteroids were used in 38 patients. Eleven patients were treated with a Janus Kinase inhibitor (jakinib) inhibitor, eight with tofacitinib, and three with an unspecified jakinib. However, 3 of the 11 patients experienced exacerbations after treatment. CONCLUSION: AA after COVID-19 vaccination is rare, and physicians should be aware of this phenomenon to improve early diagnosis and appropriate treatment.
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Alopecia Areata , Vacunas contra la COVID-19 , COVID-19 , Humanos , Alopecia Areata/inducido químicamente , Vacunas contra la COVID-19/efectos adversos , COVID-19/prevención & control , COVID-19/complicaciones , COVID-19/epidemiología , SARS-CoV-2/inmunología , Masculino , FemeninoRESUMEN
To the best of our knowledge, N6-Methyladenosine (m6A) exerts a significant role in the occurrence and development of various tumors. Gastric cancer (GC), originating from the mucosal epithelium in the digestive tract, is the fifth most common cancer and the third most common cause of cancer death around the world. Therefore, it is urgent to explore the specific mechanism of tumorigenesis of GC. As we all know, m6A modification as the most common RNA modification, is involved in the modification of mRNA and ncRNA at the post-transcriptional level, which played a regulatory role in various biological processes. As identified by numerous studies, the m6A modification are able to influence the proliferation, apoptosis, migration, and invasion of GC. What's more, m6A modification are associated with EMT, drug resistance, and aerobic glycolysis in GC. m6A related-ncRNAs may be a valuable biomarker used by the prediction of GC diagnosis in the future. This review summarizes the role of m6A modification in the mechanism of gastric cancer, with the aim of identifying biological progress.
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BACKGROUND: The FORZA trial (FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty) prospectively compared the use of fractional flow reserve (FFR) or optical coherence tomography (OCT) for treatment decisions and percutaneous coronary intervention (PCI) optimization in patients with angiographically intermediate coronary lesions. Murray law-based quantitative-flow-ratio (µQFR) is a novel noninvasive method for the computation of FFR. In the present study, we evaluated the clinical impact of µQFR, FFR, or OCT guidance in FORZA trial lesions at 3-year follow-up. METHODS: µQFR was assessed at baseline and, in the case of a decision to intervene, after (FFR- or OCT-guided) PCI. The baseline µQFR was considered the final µQFR for deferred lesions, and post-PCI µQFR value was taken as final for stented lesions. The primary end point was target vessel failure ([TVF]; cardiac death, target-vessel-related myocardial infarction, and target-vessel-revascularization) at a 3-year follow-up. RESULTS: A total of 419 vessels (199 OCT-guided and 220 FFR-guided) were included in the FORZA trial. µQFR was evaluated in 256 deferred lesions and 159 treated lesions (98 OCT-guided PCI and 61 FFR-guided PCI). In treated lesions, post-PCI µQFR was higher in OCT-group compared with FFR-group (median, 0.93 versus 0.91; P=0.023), and the post-PCI µQFR improvement was greater in FFR-group (0.14 versus 0.08; P<0.0001). At 3-year follow-up, OCT- and FFR-guided treatment decisions resulted in comparable TVF rate (6.7% versus 7.9%; P=0.617). Final µQFR was the only predictor of TVF. µQFR ≤0.89 was associated with 3× increase in TVF (11.6% versus 3.7%; P=0.004). PCI was a predictor of higher final µQFR (odds ratio, 0.22 [95% CI, 0.14-0.34]; P<0.001). CONCLUSIONS: In vessels with angiographically intermediate coronary lesions, OCT-guided PCI resulted in comparable clinical outcomes as FFR-guided PCI. µQFR estimated at the end of diagnostic or interventional procedure predicted 3-year TVF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01824030.
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Angiografía Coronaria , Estenosis Coronaria , Vasos Coronarios , Reserva del Flujo Fraccional Miocárdico , Intervención Coronaria Percutánea , Valor Predictivo de las Pruebas , Tomografía de Coherencia Óptica , Humanos , Masculino , Femenino , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/terapia , Estenosis Coronaria/fisiopatología , Intervención Coronaria Percutánea/efectos adversos , Anciano , Resultado del Tratamiento , Persona de Mediana Edad , Factores de Tiempo , Estudios Prospectivos , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Cateterismo Cardíaco , Toma de Decisiones Clínicas , Índice de Severidad de la Enfermedad , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/fisiopatología , Factores de Riesgo , StentsRESUMEN
Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+ and produce O2, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.
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BACKGROUND: Despite growing attention from researchers and governments, challenges persist in comprehensively assessing urban sound quality by integrating both quietness and naturalness aspects. GOALS: This study aimed to develop an innovative soundscape quality index that concurrently evaluates quietness and naturalness in urban soundscapes. Our objectives included conducting urban soundscape quality mapping, analyzing influential mechanisms, and identifying priority zones for sound environment management. APPROACHES: We collected sound pressure level (SPL) and raw audio data, from which we computed a normalized difference soundscape index (NDSI). With a dataset comprising 28 explanatory variables encompassing land use, built environment, vegetation characteristics, and temporal factors, we employed the random forest (RF) model to predict 10 indicators, including eight SPL-related indices, NDSI, and the QNS (quietness and naturalness soundscape) index. Crucially, we utilized SHAP (SHapley Additive exPlanations) values to interpret the RF model. FINDINGS: Spatial variations in quietness and naturalness were evident, closely associated with road networks and vegetation, respectively, with discernible temporal variations. The top three variables influencing QNS were distance to major roads, normalized difference vegetation index (NDVI), and proportion of tree coverage. Moreover, interaction effects highlighted dual negative or synergistic promoting effects on QNS from factors such as road width, human disturbance, vegetation configurations, and land cover. Notably, these mechanisms were successfully applied to six typical tourist attractions in Xiamen city, where five types of management zones were mapped based on priority considerations of population density and soundscape quality. Interestingly, natural soundscape reserves were highly correlated with city parks, high-risk zones predominantly overlapped with road networks, and potential zones comprised inner communities between streets. SIGNIFICANCE: The framework demonstrated effectiveness in mapping, exploring mechanisms, and guiding management strategies for the urban sound environment.
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Ciudades , Ruido , Humanos , Entorno Construido , Monitoreo del Ambiente/métodos , Sonido , Conservación de los Recursos Naturales/métodosRESUMEN
Background: Capsaicin is the main compound found in chili pepper and has complex pharmacologic effects. This study aimed to elucidate the mechanism of the effect of capsaicin on physiological processes by analyzing changes in metabolites and metabolic pathways. Methods: Female C57BL/6 mice were divided into two groups(n = 10/group) and fed with capsaicin-soybean oil solution(group T) or soybean oil(group C) for 6 weeks. Ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS) based metabolomics was undertaken to assess plasma and skin metabolic profile changes and identify differential metabolites through multivariate analysis. Results: According to the OPLS-DA score plots, the plasma and skin metabolic profiles in the group T and group C were significantly separated. In plasma, 38 significant differential metabolites were identified. KEGG pathway enrichment analysis revealed that the most significant plasma metabolic pathways included pyruvate metabolism and ABC transporters. In skin, seven significant differential metabolites were found. Four metabolic pathways with p values < 0.05 were detected, including sphingolipid metabolism, sphingolipid signaling pathway, apoptosis, and necroptosis. Conclusion: These findings will provide metabolomic insights to assess the physiological functions of capsaicin and contribute to a better understanding of the potential effects of a capsaicin-rich diet on health.
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Capsaicina , Aceite de Soja , Ratones , Animales , Femenino , Cromatografía Líquida de Alta Presión/métodos , Ratones Endogámicos C57BL , Metabolómica/métodos , Metaboloma , Esfingolípidos , Biomarcadores/metabolismoRESUMEN
The micro-deformation monitoring radar is usually based on Permanent Scatterer (PS) technology to realize deformation inversion. When the region is continuously monitored for a long time, the radar image amplitude and pixel variance will change significantly with time. Therefore, it is difficult to select phase-stable scatterers by conventional amplitude deviation methods, as they can seriously affect the accuracy of deformation inversion. For different regions studied within the same scenario, using a PS selection method based on the same threshold often increases the size of the deformation error. Therefore, this paper proposes a new PS selection method based on the Gaussian Mixture Model (GMM). Firstly, PS candidates (PSCs) are selected based on the pixels' amplitude information. Then, the amplitude deviation index of each PSC is calculated, and each pixel's probability values in different Gaussian distributions are acquired through iterations. Subsequently, the cluster types of pixels with larger probability values are designated as low-amplitude deviation pixels. Finally, the coherence coefficient and phase stability of low-amplitude deviation pixels are calculated. By comparing the probability values of each of the pixels in different Gaussian distributions, the cluster type with the larger probability, such as high-coherence pixels and high-phase stability pixels, is selected and designated as the final PS. Our analysis of the measured data revealed that the proposed method not only increased the number of PSs in the group, but also improved the stability of the number of PSs between groups.
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Anticuerpos Monoclonales Humanizados , Proteínas Adaptadoras de Señalización CARD , Guanilato Ciclasa , Humanos , Proteínas Adaptadoras de Señalización CARD/genética , Anticuerpos Monoclonales Humanizados/uso terapéutico , Guanilato Ciclasa/genética , Proteínas de la Membrana/genética , Fenotipo , Enfermedades Cutáneas Papuloescamosas/tratamiento farmacológico , Enfermedades Cutáneas Papuloescamosas/patología , Enfermedades Cutáneas Papuloescamosas/genética , Fármacos Dermatológicos/uso terapéutico , Masculino , FemeninoRESUMEN
BACKGROUND: Coronary angiography-derived radial wall strain (RWS) is a newly developed index that can be readily accessed and describes the biomechanical features of a lesion. OBJECTIVES: The authors sought to investigate the association of RWS with fractional flow reserve (FFR) and high-risk plaque (HRP), and their relative prognostic implications. METHODS: We included 484 vessels (351 patients) deferred after FFR measurement with available RWS data and coronary computed tomography angiography. On coronary computed tomography angiography, HRP was defined as a lesion with both minimum lumen area <4 mm2 and plaque burden ≥70%. The primary outcome was target vessel failure (TVF), a composite of target vessel revascularization, target vessel myocardial infarction, or cardiac death. RESULTS: The mean FFR and RWSmax were 0.89 ± 0.07 and 11.2% ± 2.5%, respectively, whereas 27.7% of lesions had HRP, 15.1% had FFR ≤0.80. An increase in RWSmax was associated with a higher risk of FFR ≤0.80 and HRP, which was consistent after adjustment for clinical or angiographic characteristics (all P < 0.05). An increment of RWSmax was related to a higher risk of TVF (HR: 1.23 [95% CI: 1.03-1.47]; P = 0.022) with an optimal cutoff of 14.25%. RWSmax >14% was a predictor of TVF after adjustment for FFR or HRP components (all P < 0.05) and showed a direct prognostic effect on TVF, not mediated by FFR ≤0.80 or HRP in the mediation analysis. When high RWSmax was added to FFR ≤0.80 or HRP, there were increasing outcome trends (all P for trend <0.001). CONCLUSIONS: RWS was associated with coronary physiology and plaque morphology but showed independent prognostic significance.
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Reserva del Flujo Fraccional Miocárdico , Humanos , Angiografía Coronaria , Resultado del Tratamiento , Corazón , Angiografía por Tomografía ComputarizadaRESUMEN
Purpose: Porokeratosis (PK) is a chronic autosomal-dominant cutaneous keratinization disorder exhibiting clinical and genetic heterogeneity. Mevalonate decarboxylase (MVD), farnesyl diphosphate synthase (FDPS), phosphomevalonate kinase(PMVK), and mevalonate kinase genes(MVK), which encode the mevalonate pathway, are disease-causing genes in PK. Patients and Methods: Data and blood samples were collected from two Chinese families and five sporadic patients with porokeratosis. Whole-exome and Sanger sequencing were performed to detect pathogenic gene mutation in the patients. Results: Five heterozygous mutations were identified, including a novel FDPS stop-gain mutation c.438T>G (p.Tyr146Ter), a novel MVD missense mutation c.683G>C (p.R228P), and three previously reported MVD mutations: c.746T>C (p.F249S), c.875A>G (p.N292S), and c.1111_1113del (p.371_371del). The novel FDPS c.438T>G mutation was predicted as "disease-causing" (p = 1) by Mutation Taster. The other novel MVD c.683G>C was also predicted as "deleterious" (score = 0.00) by Sorting Intolerant From Tolerant (SIFT), "probably damaging" (score = 1) by PolyPhen2, and "disease-causing" (p = 0.999) by Mutation Taster. Conclusion: Our results extended the mutation spectrum of mevalonate pathway genes in porokeratosis and provided useful strategies for a more accurate diagnosis and genetic counseling.
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Secondary development is a key biological characteristic of woody plants and the basis of wood formation. Exogenous nitrogen can affect the secondary growth of poplar, and some regulatory mechanisms have been found in the secondary xylem. However, the effect of nitrogen on cambium has not been reported. Herein, we investigated the effects of different nitrogen concentrations on cambium development using combined transcriptome and metabolome analysis. The results show that, compared with 1 mM NH4NO3 (M), the layers of hybrid poplar cambium cells decreased under the 0.15 mM NH4NO3 (L) and 0.3 mM NH4NO3 (LM) treatments. However, there was no difference in the layers of hybrid poplar cambium cells under the 3 mM NH4NO3 (HM) and 5 mM NH4NO3 (H) treatments. Totals of 2365, 824, 649 and 398 DEGs were identified in the M versus (vs.) L, M vs. LM, M vs. HM and M vs. H groups, respectively. Expression profile analysis of the DEGs showed that exogenous nitrogen affected the gene expression involved in plant hormone signal transduction, phenylpropanoid biosynthesis, the starch and sucrose metabolism pathway and the ubiquitin-mediated proteolysis pathway. In M vs. L, M vs. LM, M vs. HM and M vs. H, differential metabolites were enriched in flavonoids, lignans, coumarins and saccharides. The combined analysis of the transcriptome and metabolome showed that some genes and metabolites in plant hormone signal transduction, phenylpropanoid biosynthesis and starch and sucrose metabolism pathways may be involved in nitrogen regulation in cambium development, whose functions need to be verified. In this study, from the point of view that nitrogen influences cambium development to regulate wood formation, the network analysis of the transcriptome and metabolomics of cambium under different nitrogen supply levels was studied for the first time, revealing the potential regulatory and metabolic mechanisms involved in this process and providing new insights into the effects of nitrogen on wood development.
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Cámbium , Populus , Cámbium/genética , Reguladores del Crecimiento de las Plantas , Transcriptoma , Metaboloma , Nitrógeno , Populus/genética , Almidón , SacarosaRESUMEN
Before menopause, females exhibit a lower incidence of cardiovascular disease than age-matched males, possibly owing to the protective effects of sex hormones. 17ß-estradiol (17ß-E2) protects against oxidative stress-induced injury by suppressing thrombospondin-1 (THBS1) expression in endothelial cells. Here, we examined the role of 17ß-E2-mediated THBS1 suppression in preventing cell senescence and apoptosis. Human umbilical vein endothelial cells (HUVECs) were cultivated and treated with siRNA or overexpression plasmids to regulate THBS1. H2O2, estrogen-activity modulating drugs, and LY2109761 (a TGF-ß kinase inhibitor) treatments were applied. THBS1 knockdown repressed, and its overexpression aggravated, H2O2-induced cell injury, affecting cell death, proliferation, senescence, and apoptosis. 17ß-E2 inhibited THBS1 mRNA and protein expression time- and dose-dependently, by targeting ERß. THBS1 overexpression blocked 17ß-E2 from preventing H2O2-induced injury, significantly activating the TGF-ß/Smad pathway. 17ß-E2 inhibited H2O2-induced oxidative stress by downregulating THBS1 expression and TGF-ß/Smad signaling in HUVECs. The THBS1/TGF-ß/Smad axis could thus be a therapeutic target.
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Peróxido de Hidrógeno , Factor de Crecimiento Transformador beta , Femenino , Humanos , Células Endoteliales de la Vena Umbilical Humana , Peróxido de Hidrógeno/toxicidad , Peróxido de Hidrógeno/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Estradiol/farmacología , Estradiol/metabolismo , Estrógenos/metabolismo , ApoptosisRESUMEN
BACKGROUND: Oral squamous cell carcinoma (OSCC) is an infiltrative malignancy characterized by a significantly elevated recurrence rate. Dickkopf-related protein 1 (DKK1), which plays an oncogene role in many cancers, acts as an inhibitor of the Wingless protein (Wnt) signaling pathway. Currently, there is a lack of consensus regarding the role of DKK1 in OSCC or its clinical significance. OBJECTIVE: To examine the role and effect of DKK1 in OSCC. METHODS: The identification of differentially expressed genes (DEGs) in OSCC was conducted by utilizing databases such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A comprehensive analysis of gene expression profile interactions (GEPIA) and Kaplan-Meier curve were conducted to investigate the associations among DEGs, patient survival and prognosis in individuals with OSCC. The biological function of DKK1 in OSCC was investigated by using molecular biology approaches. RESULTS: The expression of DKK1 was found to be upregulated in OSCC tissues at various stages. High levels of DKK1 expression exhibited a positive correlation with the overall survival (OS) and progression-free survival (PFS) rates among OSCC patients. DKK1 knockdown suppressed the proliferation and induced apoptotic response in OSCC cells. Moreover, DKK1 exerted a positive regulatory effect on HMGA2 expression, thereby modulating cell growth and apoptosis in OSCC. The expression of DKK1 was found to be positively correlated with the infiltration of immune cells in patients with OSCC. Additionally, higher levels of CD4+ T cells were associated with improved 5-year survival rates. CONCLUSION: DKK1 is a prognostic biomarker for patients with OSCC.
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Ecosystem restoration has traditionally focused on re-establishing vegetation and other foundation species at basal trophic levels, with mixed outcomes. Here, we show that threatened shorebirds could be important to restoring coastal wetland multifunctionality. We carried out surveys and manipulative field experiments in a region along the Yellow Sea affected by the invasive cordgrass Spartina alterniflora. We found that planting native plants alone failed to restore wetland multifunctionality in a field restoration experiment. Shorebird exclusion weakened wetland multifunctionality, whereas mimicking higher predation before shorebird population declines by excluding their key prey - crab grazers - enhanced wetland multifunctionality. The mechanism underlying these effects is a simple trophic cascade, whereby shorebirds control crab grazers that otherwise suppress native vegetation recovery and destabilize sediments (via bioturbation). Our findings suggest that harnessing the top-down effects of shorebirds - through habitat conservation, rewilding, or temporary simulation of consumptive or non-consumptive effects - should be explored as a nature-based solution to restoring the multifunctionality of degraded coastal wetlands.
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Braquiuros , Humedales , Animales , Ecosistema , Poaceae/metabolismo , PlantasRESUMEN
Exogenous nitrogen and carbon can affect plant cell walls, which are composed of structural carbon. Sucrose synthase (SUS), invertase (INV), hexokinase (HXK), phosphoglucomutase (PGM), and UDP-glucose pyrophosphorylase (UGP) are the key enzymes of sucrose metabolism involved in cell wall synthesis. To understand whether these genes are regulated by carbon and nitrogen to participate in structural carbon biosynthesis, we performed genome-wide identification, analyzed their expression patterns under different carbon and nitrogen treatments, and conducted preliminary functional verification. Different concentrations of nitrogen and carbon were applied to poplar (Populus trichocarpa Torr. and Gray), which caused changes in cellulose, lignin, and hemicellulose contents. In poplar, 6 SUSs, 20 INVs, 6 HXKs, 4 PGMs, and 2 UGPs were identified. Moreover, the physicochemical properties, collinearity, and tissue specificity were analyzed. The correlation analysis showed that the expression levels of PtrSUS3/5, PtrNINV1/2/3/5/12, PtrCWINV3, PtrVINV2, PtrHXK5/6, PtrPGM1/2, and PtrUGP1 were positively correlated with the cellulose content. Meanwhile, the knockout of PtrNINV12 significantly reduced the cellulose content. This study could lay the foundation for revealing the functions of SUSs, INVs, HXKs, PGMs, and UGPs, which affected structural carbon synthesis regulated by nitrogen and carbon, proving that PtrNINV12 is involved in cell wall synthesis.
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Populus , Populus/metabolismo , Celulosa/metabolismo , Lignina/metabolismo , Carbono/metabolismo , Nitrógeno/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Although the enrichment of resistance genes in soil has been explored in recent years, there are still some key questions to be addressed regarding the variation of ARG composition in soil with different fertilization treatments, such as the core ARGs in soil after different fertilization treatments, the correlation between ARGs and bacterial taxa, etc. For soils after different fertilization treatments, the distribution and combination of ARG in three typical fertilization methods (organic fertilizer alone, chemical fertilizer alone, and conventional fertilizer) and non-fertilized soils were investigated in this study using high-throughput fluorescence quantitative PCR (HT-qPCR) technique. The application of organic fertilizers significantly increased the abundance and quantity of ARGs and their subtypes in the soil compared to the non-fertilized soil, where sul1 was the ARGs specific to organic fertilizers alone and in higher abundance. The conventional fertilizer application also showed significant enrichment of ARGs, which indicated that manure addition often had a more decisive effect on ARGs in soil than chemical fertilizers, and three bacteria, Pseudonocardia, Irregularibacter, and Castllaniella, were the key bacteria affecting ARG changes in soil after fertilization. In addition, nutrient factors and heavy metals also affect the distribution of ARGs in soil and are positively correlated. This paper reveals the possible reasons for the increase in the number of total soil ARGs and their relative abundance under different fertilization treatments, which has positive implications for controlling the transmission of ARGs through the soil-human pathway.
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As a result of abnormal wound healing in susceptible individuals, keloids are characterized by hyperproliferation of fibroblasts and excessive deposition of the extracellular matrix (ECM). Current surgical and therapeutic modalities provide limited satisfactory results. Circular ribonucleic acids (circRNAs) play a crucial role in the pathogenesis of various fibrotic diseases, but the potential biological function and expression profile of circRNAs in keloid formation remain unknown. In this study, we explored the function of circFoxp1 on keloid formation. Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) results revealed that circFoxp1 expression was higher in the keloid tissues. Furthermore, RNA-fluorescence in situ hybridization (RNA-FISH) and RNAscope illustrated that circFoxp1 was present in the cytoplasm. Subsequent cellular experiments demonstrated that circFoxp1 overexpression enhanced proliferation, migration, and ECM deposition. In addition, apoptosis was inhibited. Cell proliferation, inflammatory response, and oxidative phosphorylation of fibroblasts were also observed by RNA sequencing and were closely related to scar formation. The therapeutic potential of circFoxp1 was investigated by establishing keloid implantation models. In vivo, circFoxp1 can promote fibroblast proliferation and ECM deposition. RNA pull-down and western blot assays verified the interaction of circFoxp1 with RACK1. The present study reveals that circFoxp1 contributes to the pathological hyperplasia of keloid, which may improve inflammation and cell proliferation. Our data indicate that circFoxp1 may serve as a novel, promising therapeutic target, presenting a new avenue for understanding the underlying pathogenesis of keloid.
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Queloide , Humanos , Queloide/genética , Regulación hacia Arriba , ARN Circular/genética , ARN Circular/metabolismo , Hibridación Fluorescente in Situ , Proliferación Celular/genética , Fibroblastos/metabolismoRESUMEN
The WRKY transcription factor (TF) family is one the largest plant-specific transcription factor families. It has been proven to play significant roles in multiple plant biological processes, especially stress response. Although many WRKY TFs have been identified in various plant species, WRKYs in white birch (Betula platyphylla Suk.) remain to be studied. Here, we identified a total of 68 BpWRKYs, which could be classified into four main groups. The basic physiochemical properties of these TFs were analyzed using bioinformatics tools, including molecular weight, isoelectric point, chromosome location, and predicted subcellular localization. Most BpWRKYs were predicted to be located in the nucleus. Synteny analysis found 17 syntenic gene pairs among BpWRKYs and 52 syntenic gene pairs between BpWRKYs and AtWRKYs. The cis-acting elements in the promoters of BpWRKYs could be enriched in multiple plant biological processes, including stress response, hormone response, growth and development, and binding sites. Tissue-specific expression analysis using qRT-PCR showed that most BpWRKYs exhibited highest expression levels in the root. After ABA, salt (NaCl), or cold treatment, different BpWRKYs showed different expression patterns at different treatment times. Furthermore, the results of the Y2H assay proved the interaction between BpWRKY17 and a cold-responsive TF, BpCBF7. By transient expression assay, BpWRKY17 and BpWRKY67 were localized in the nucleus, consistent with the previous prediction. Our study hopes to shed light for research on WRKY TFs and plant stress response.
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Proteínas de Plantas , Factores de Transcripción , Factores de Transcripción/metabolismo , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genética , Betula/genética , Betula/metabolismo , Regulación de la Expresión Génica de las Plantas , FilogeniaRESUMEN
BACKGROUND: Leucine-rich repeat-containing protein 59 (LRRC59) is an endoplasmic reticulum membrane protein involved in various cancers, but its role in bladder cancer (BC) has not been reported. The aim of the present study was to investigate the role of LRRC59 protein in BC progression and prognosis. METHODS: The expression profile and clinical significance were retrieved from BC patients in the Cancer Genome Atlas database. The methylation status of LRRC59 was analyzed by UALCAN and MethSurv databases. Potential signaling pathways and biological functions were explored by functional enrichment analysis. Immunocyte infiltration was evaluated by CIBERSORT analysis. The prognostic value of LRRC59 was evaluated by Kaplan-Meier and Cox regression analyses. Overall survival (OS) was predicted by the nomogram plot established in this study. LRRC59 expression in 10 pairs BC and adjacent noncancerous tissues were analyzed by immunohistochemistry (IHC). Cell proliferation, migration, and invasion were detected by CCK8, colony formation assay, transwell assay, and cell scratch assay, respectively. Proteins related to epithelial-mesenchymal transition and apoptosis were detected by western blot. RESULTS: LRRC59 overexpression significantly decreased OS, disease-specific survival, and progress-free interval of BC patients. LRRC59 was a prognostic marker for OS and its hypomethylation status signified a poor prognosis. LRRC59 overexpression was correlated with infiltration of resting memory CD4 T cells, memory activated CD4 T cells, resting NK cells, macrophages M0, M1, M2, and neutrophils. IHC showed that the LRRC59 expression in BC tissue was significantly higher than that in adjacent noncancerous tissue. Knockdown of LRRC59 expression inhibited the proliferation of BC cells and reduced their migratory ability. Western blot showed that Snail and vimentin protein expressions decreased, while E-cadherin expressions increased. CONCLUSIONS: LRRC59 expression can predict the outcome of BC independently and serve as a new biomarker for diagnosis.
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Biomarcadores de Tumor , Neoplasias de la Vejiga Urinaria , Humanos , Biomarcadores de Tumor/metabolismo , Estimación de Kaplan-Meier , Proteínas de la Membrana/genética , Pronóstico , Vejiga Urinaria/química , Neoplasias de la Vejiga Urinaria/diagnósticoRESUMEN
Liver fibrosis is a chronic inflammatory process characterized by the accumulation of extracellular matrix (ECM), which contributes to cirrhosis and hepatocellular carcinoma. Increasing evidence suggests that the activation of hepatic stellate cells (HSCs) under an inflammatory state leads to the secretion of collagens, which can cause cirrhosis. In this study, we analysed data from the Gene Expression Omnibus (GEO) databases to identify differentially expressed genes (DEGs) between quiescent and fibrotic HSCs. We found that Microfibril Associated Protein 2 (MFAP2) was elevated in carbon tetrachloride (CCl4)-induced liver fibrosis and Transforming Growth Factor-Beta 1 (TGF-ß1)-activated HSCs. Knockdown of MFAP2 inhibited HSC proliferation and partially attenuated TGF-ß-stimulated fibrogenesis markers. Bioinformatics analysis revealed that Fibrillin-1 (FBN1) was correlated with MFAP2, and the expression of FBN1 was significantly upregulated after MFAP2 overexpression. Silencing MFAP2 partially attenuated the activation of HSCs by inhibiting HSC proliferation and decreasing collagen deposits. In vitro results showed that the inhibition of MFAP2 alleviated hepatic fibrosis by inhibiting the activation and inducing the apoptosis of active HSCs in a CCl4-induced mouse model. In conclusion, our results suggest that MFAP2 is a potential target for the clinical treatment of liver fibrosis.