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Dnttip2 is one of the components of the small subunit (SSU) processome. In yeast, depletion of dnttip2 leads to an inefficient processing of pre-rRNA and a decrease in synthesis of the mature 18S rRNA. However, the biological roles of Dnttip2 in higher organisms are poorly defined. In this study, we demonstrate that dnttip2 is a maternal gene in zebrafish. Depletion of Dnttip2 leads to embryonic lethal with severe digestive organs hypoplasia. The loss of function of Dnttip2 also leads to partial defects in cleavage at the A0-site and E-site during 18S rRNA processing. In conclusion, Dnttip2 is essential for 18S rRNA processing and digestive organ development in zebrafish.
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Pez Cebra , Animales , Procesamiento Postranscripcional del ARN , ARN Ribosómico 18S/genética , Saccharomyces cerevisiae/metabolismo , Pez Cebra/genética , Pez Cebra/metabolismoRESUMEN
Activating the stimulator of the interferon gene (STING) is a promising immunotherapeutic strategy for converting "cold" tumor microenvironment into "hot" one to achieve better immunotherapy for malignant tumors. Herein, a manganese-based nanotransformer is presented, consisting of manganese carbonyl and cyanine dye, for MRI/NIR-II dual-modality imaging-guided multifunctional carbon monoxide (CO) gas treatment and photothermal therapy, along with triggering cGAS-STING immune pathway against triple-negative breast cancer. This nanosystem is able to transfer its amorphous morphology into a crystallographic-like formation in response to the tumor microenvironment, achieved by breaking metal-carbon bonds and forming coordination bonds, which enhances the sensitivity of magnetic resonance imaging. Moreover, the generated CO and photothermal effect under irradiation of this nanotransformer induce immunogenic death of tumor cells and release damage-associated molecular patterns. Simultaneously, the Mn acts as an immunoactivator, potentially stimulating the cGAS-STING pathway to augment adaptive immunity, resulting in promoting the secretion of type I interferon, the proliferation of cytotoxic T lymphocytes and M2-macrophages repolarization. This nanosystem-based gas-photothermal treatment and immunoactivating therapy synergistic effect exhibit excellent antitumor efficacy both in vitro and in vivo, reducing the risk of triple-negative breast cancer recurrence and metastasis; thus, this strategy presents great potential as multifunctional immunotherapeutic agents for cancer treatment.
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Inmunoterapia , Manganeso , Terapia Fototérmica , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/terapia , Inmunoterapia/métodos , Manganeso/química , Humanos , Animales , Terapia Fototérmica/métodos , Línea Celular Tumoral , Femenino , Imagen por Resonancia Magnética/métodos , Ratones , Microambiente Tumoral , Nanopartículas/química , Fototerapia/métodosRESUMEN
The dichloromethane fraction of Kadsura heteroclita roots was separated and purified by chromatographic techniques(e.g., silica gel, Sephadex LH-20, ODS, MCI column chromatography) and semi-preparative HPLC. Twenty compounds were isolated from K. heteroclita, and their structures were identified by NMR, MS, UV, and X-ray single crystal diffraction techniques. Twenty compounds were isolated from K. heteroclita, which were identified as xuetongdilactone G(1), mallomacrostin C(2), 3,4-seco(24Z)-cychmrt-4(28),24-diene-3,26-dioic acid 3-methyl ester(3), nigranoic acid(4), methyl ester schizanlactone E(5), schisandronic acid(6), heteroclic acid(7), wogonin(8),(2R,3R)-4'-O-methyldihydroquercetin(9), 15,16-bisnor-13-oxo-8(17),11E-labdadien-19-oic acid(10), stigmast-4-ene-6ß-ol-3-one(11), psoralen(12),(1R,2R,4R)-trihydroxy-p-menthane(13), homovanillyl alcohol(14), 2-(4-hydroxyphenyl)-ethanol(15), coniferaldehyde(16),(E)-7-(4-hydroxy-3-methoxyphenyl)-7-methylbut-8-en-9-one(17), acetovanillone(18), vanillic acid(19) and vanillin(20). Compound 1 is a new compound named xuetongdilactone G. Compounds 2-3 and 8-20 are isolated from K. heteroclita for the first time.
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Kadsura , Kadsura/química , Espectroscopía de Resonancia Magnética , Raíces de Plantas/química , Ésteres/análisisRESUMEN
Norditerpenes are considered to be a common and widely studied class of bioactive compounds in plants, exhibiting a wide array of complex and diverse structural types and originating from various sources. Based on the number of carbons, norditerpenes can be categorized into C19, C18, C17, and C16 compounds. Up to now, 557 norditerpenes and their derivatives have been found in studies published between 2010 and 2023, distributed in 51 families and 132 species, with the largest number in Lamiaceae, Euphorbiaceae, and Cephalotaxaceae. These norditerpenes display versatile biological activities, including anti-tumor, anti-inflammatory, antimicrobial, and antioxidant properties, as well as inhibitory effects against HIV and α-glucosidase, and can be considered as an important source of treatment for a variety of diseases that had a high commercial value. This review provides a comprehensive summary of the plant sources, chemical structures, and biological activities of norditerpenes derived from natural sources, serving as a valuable reference for further research development and application in this field.
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Diterpenos , Euphorbiaceae , Lamiaceae , Humanos , Antioxidantes/farmacología , CarbonoRESUMEN
OBJECTIVES: This study aims to test the reliability and validity of the Chinese version of the Asher-McDade aesthetic index and clarify its feasibility for the postoperative outcome evaluation of cleft lip in China. METHODS: The Chinese version of the Asher-McDade aesthetic index was established through translation, back translation, debugging, and pre-survey. Eighty postoperative photographs of patients with cleft lip admitted to the West China Hospital of Stomatology, Sichuan University were included. Ten healthcare professionals, including surgeons, nurses, and students, in the department of cleft lip and palate surgery finished the index to test its reliability and validity. RESULTS: The Cronbach's alpha coefficient and retest reliability of this index are 0.804 and 0.895, respectively. The item-level content validity index (I-CVI) and scale-level content validity index ave-rage (S-CVI/ave) of the index are 1.000 and 0.95, respectively. For this index, the Kaiser-Meyer-Olkin (KMO) test score is 0.706, the χ2 value of Bartlett's test for the consistency of the index is 962.260 (P<0.01), and the cumulative variance contribution rate is 63.095%. CONCLUSIONS: The Chinese version of the Asher-McDade aesthe-tic index has good reliability and validity and is applicable to the professional evaluation of the effect of postoperative photographs in Chinese patients with cleft lip.
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Labio Leporino , Fisura del Paladar , Humanos , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Reproducibilidad de los Resultados , Estética Dental , Evaluación de Resultado en la Atención de Salud , China , Psicometría , Encuestas y CuestionariosRESUMEN
Spasmodic torticollis (ST) is a focal dystonia that affects adults, causing limited muscle control and impacting daily activities and quality of life. The etiology and curative methods for ST remain unclear. Botulinum toxin is widely used as a first-line treatment, but long-term usage can result in reduced tolerance and adverse effects. Rehabilitation therapy, with its minimal side effects and low potential for harm, holds significant clinical value. This article explores the effectiveness of adjunctive therapies, including exercise therapy, transcranial magnetic stimulation, shockwave therapy, neuromuscular electrical stimulation, vibration therapy, electromyographic biofeedback, and acupuncture, in the treatment of ST. The aim is to provide clinicians with additional treatment options and to discuss the efficacy of rehabilitation therapy for ST.
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Objective: Sepsis is linked to high morbidity and mortality rates. Consequently, early diagnosis is crucial for proper treatment, reducing hospitalization, and mortality rates. Additionally, over one-fifth of sepsis patients still face a risk of death. Hence, early diagnosis, and effective treatment play pivotal roles in enhancing the prognosis of patients with sepsis. Method: The study analyzed whole blood data obtained from patients with sepsis and control samples sourced from three datasets (GSE57065, GSE69528, and GSE28750). Commonly dysregulated immune-related genes (IRGs) among these three datasets were identified. The differential characteristics of these common IRGs in the sepsis and control samples were assessed using the REO-based algorithm. Based on these differential characteristics, samples from eight Gene Expression Omnibus (GEO) databases (GSE57065, GSE69528, GSE28750, GSE65682, GSE69063, GSE95233, GSE131761, and GSE154918), along with three ArrayExpress databases (E-MTAB-4421, E-MTAB-4451, and E-MTAB-7581), were categorized and scored. The effectiveness of these differential characteristics in distinguishing sepsis samples from control samples was evaluated using the AUC value derived from the receiver operating characteristic curve (ROC) curve. Furthermore, the expression of IRGs was validated in peripheral blood samples obtained from patients with sepsis through qRT-PCR. Results: Among the three training datasets, a total of 84 common dysregulated immune-related genes (IRGs) were identified. Utilizing a within-sample relative expression ordering (REOs)-based algorithm to analyze these common IRGs, differential characteristics were observed in three reverse stable pairs (ELANE-RORA, IL18RAP-CD247, and IL1R1-CD28). In the eight GEO datasets, the expression of ELANE, IL18RAP, and IL1R1 demonstrated significant upregulation, while RORA, CD247, and CD28 expression exhibited notable downregulation during sepsis. These three pairs of immune-related marker genes displayed accuracies of 95.89% and 97.99% in distinguishing sepsis samples among the eight GEO datasets and the three independent ArrayExpress datasets, respectively. The area under the receiver operating characteristic curve ranged from 0.81 to 1.0. Additionally, among these three immune-related marker gene pairs, mRNA expression levels of ELANE and IL1R1 were upregulated, whereas the levels of CD247 and CD28 mRNA were downregulated in blood samples from patients with sepsis compared to normal controls. Conclusion: These three immune-related marker gene pairs exhibit high predictive performance for blood samples from patients with sepsis. They hold potential as valuable auxiliary clinical blood screening tools for sepsis.
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This study aimed to validate the predictors of speech outcomes following Furlow palatoplasty in patients with velopharyngeal insufficiency (VPI) after primary palatoplasty and to propose and validate a model to predict the risk of persistent VPI. The study included patients with VPI after primary palatoplasty who underwent Furlow palatoplasty as a secondary surgery. Eleven variables were included: velar length, pharyngeal cavity depth, velopharyngeal gap, velopharyngeal closure pattern, sex, presence of cleft lip, existence of palatal fistula, surgeon, age at primary palatoplasty, age at secondary surgery, and time interval between primary palatoplasty and secondary surgery. Postoperative speech outcomes were assessed at least 1 year after the secondary surgery and classified as velopharyngeal competence (VPC) or VPI. Variables were analyzed using multivariate logistic regression analysis, and the area under the curve (AUC) was used to validate model accuracy. The study sample comprised 101 patients. Of the patients, 62 had VPC and 39 had VPI after secondary surgery. The results showed a younger age at secondary surgery, a smaller velopharyngeal gap, being female, having a coronal velopharyngeal closure pattern and a velopharyngeal closure ratio of 90% or greater produced a greater probability of VPC. Given the constraints of this study, it appears that the Furlow palatoplasty should be prioritized when the clinical model predicts a substantial likelihood of VPC post-surgery.
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Fisura del Paladar , Insuficiencia Velofaríngea , Humanos , Femenino , Masculino , Insuficiencia Velofaríngea/etiología , Insuficiencia Velofaríngea/cirugía , Habla , Paladar Blando/cirugía , Resultado del Tratamiento , Fisura del Paladar/cirugía , Fisura del Paladar/complicaciones , Estudios RetrospectivosRESUMEN
Mounting data hints that the gut microbiota's role may be pivotal in understanding the emergence of psoriasis. However, discerning a direct causal link is yet elusive. In this exploration, we adopted a Mendelian randomization (MR) strategy to probe the prospective causal interplay between the gut's microbial landscape and the predisposition to psoriasis. Genetic markers acting as instrumental variables for gut microbiota were extrapolated from a genome-wide association study (GWAS) encompassing 18,340 individuals. A separate GWAS yielded summary data for psoriasis, which covered 337,159 patients and 433,201 control subjects. The primary analysis hinged on inverse variance weighting (IVW). Additional methods like the weighted median approach and MR-Egger regression were employed to validate the integrity of our findings. Intriguing correlations emerged between psoriasis risk and eight specific bacterial traits. To illustrate: Mollicutes presented an odds ratio (OR) of 1.003 with a 95% confidence interval (CI) spanning 1.001-1.005 (p = 0.016), while the family. Victivallaceae revealed an OR of 0.998 with CI values between 0.997 and 0.999 (p = 0.023). Eubacterium (coprostanoligenes group) revealed an OR of 0.997 with CI values between 0.994 and 0.999 (p = 0.027). Eubacterium (fissicatena group) revealed an OR of 0.997 with CI values between 0.996 and 0.999 (p = 0.005). Holdemania revealed an OR of 1.001 with CI values 1-1.003 (p = 0.034). Lachnospiraceae (NK4A136 group) revealed an OR of 0.997 with CI values between 0.995 and 0.999 (p = 0.046). Lactococcus revealed an OR of 0.998 with CI values between 0.996 and 0.999 (p = 0.008). Tenericutes revealed an OR of 1.003 with CI values between 1.001 and 1.006 (p = 0.016). Sensitivity analysis for these bacterial features yielded congruent outcomes, reinforcing statistically significant ties between the eight bacterial entities and psoriasis. This comprehensive probe underscores emerging evidence pointing towards a plausible causal nexus between diverse gut microbiota and the onset of psoriasis. It beckons further research to unravel the intricacies of how the gut's microbial constituents might sway psoriasis's pathogenesis.
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Clostridiales , Eubacterium , Microbioma Gastrointestinal , Tenericutes , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Estudios ProspectivosRESUMEN
Objective: To explore the effect of varying numbers of embryo washings prior to blastocyst formation in non-invasive preimplantation chromosome screening (NICS) on the accuracy of NICS results. Methods: In this study, 68 blastocysts from preimplantation genetic testing (PGT)-assisted pregnancy were collected at our institution. On the fourth day of embryo culture, the embryos were transferred to a new medium for blastocyst culture and were washed either three times (NICS1 group) or ten times (NICS2 group). A trophectoderm (TE) biopsy was performed on the blastocysts, and the corresponding embryo culture media were collected for whole genome amplification (WGA) and high-throughput sequencing. Results: The success rate of WGA was 100% (TE biopsy), 76.7% (NICS1 group), and 89.5% (NICS2 group). The success rate of WGA in embryo medium on days 5 and 6 of culture was 75.0% (33/44) and 100% (24/24), respectively. Using TE as the gold standard, the karyotype concordance rate between the results of the NICS1 and NICS2 groups' embryo culture medium samples and TE results was 43.5% (10/23) and 73.5% (25/34), respectively. The sensitivity and specificity of detecting chromosomal abnormalities were higher in the NICS2 group than in the NICS1 group when TE was used (83.3% vs 60.0%; 62.5% vs 30.8%, respectively). The false-positive rate and false-negative rate (i.e., misdiagnosis rate and missed diagnosis rate, respectively) were lower in the NICS2 group than in the NICS1 group (37.5% vs 69.2%; 16.7% vs 40.0%, respectively). Conclusion: The NICS yielded favorable results after ten washings of the embryos. These findings provide a novel method for lowering the amount of cell-free DNA contamination from non-embryonic sources in the medium used for embryo development, optimizing the sampling procedure and improving the accuracy of the NICS test.
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Diagnóstico Preimplantación , Embarazo , Femenino , Humanos , Diagnóstico Preimplantación/métodos , Pruebas Genéticas/métodos , Blastocisto , Aberraciones Cromosómicas , CromosomasRESUMEN
Early diagnosis and treatment of renal fibrosis (RF) significantly affect the clinical outcomes of chronic kidney diseases (CKDs). As the typical fibrotic ailment, RF is characterized by remodeling of the extracellular matrix, and the activation of fibroblast activation protein (FAP) plays a crucial role in the mediation of extracellular matrix protein degradation. Therefore, FAP can serve as a biomarker for RF. However, up to now, no effective tools have been reported to diagnose early-stage RF via detecting FAP. In this work, a polymeric nanobeacon integrating an FAP-sensitive amphiphilic polymer and fluorophores was proposed, which was used to diagnose early RF by sensing FAP. The FAP can be detected in the range of 0 to 200 ng/mL with a detection limit of 0.132 ng/mL. Furthermore, the fluorescence imaging results demonstrate that the polymeric nanobeacon can sensitively image fibrotic kidneys in mice with unilateral ureteral occlusion (UUO), suggesting its potential for early RF diagnosis and guidance of FAP-targeted treatments. Importantly, when employed alongside with non-invasive diagnostic techniques like magnetic resonance imaging (MRI) and serological tests, this nanobeacon exhibits excellent biocompatibility, low biological toxicity, and sustained imaging capabilities, making it a suitable fluorescent tool for diagnosing various FAP-related fibrotic conditions. To our knowledge, this study represents the first attempt to image RF in early stage by detecting FAP, offering a promising fluorescent molecular tool for diagnosing various FAP-associated diseases in the future.
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Técnicas Biosensibles , Insuficiencia Renal Crónica , Ratones , Animales , Fibrosis , Polímeros , Fibroblastos , Diagnóstico PrecozRESUMEN
BACKGROUND: Melasma is a prevalent pigmented disease, yet its pathogenesis remains unclear, posing challenges for effective treatment. Bibliometric analysis, a novel approach to literature research, offers the opportunity to evaluate research trends through qualitative and quantitative methods. This study utilizes bibliometric methods to analyze the existing literature on melasma treatment, examining influential publications, institutions, countries, and authors through statistical analysis. METHODS: In order to retrieve manuscripts related to the topic of melasma treatment, we conducted a search using the search formula: (TS = (melasma or Chloasma or "mask of pregnancy")) AND TS = (treatment or therapy). We searched through the Web of Science Core Collection database, covering publications from 2000 to 2023. VOSviewer, CiteSpace and the Bibliometric online site (https://bibliometric.com/app) were used to conduct this bibliometric analysis. Our analysis focused on various factors including publications, authors co-authorship, institutions, countries, citation analysis, keywords co-occurrence, references co-citation and journal co-citation. RESULTS: A total of 943 articles and 200 reviews were published between 2000 and 2023, accumulating a total of 8628 citations. The average number of citations per item was 18.85, and the average number of citations per year was 292.69. The most prolific author, Sungeun Chang, contributed a total of 9 articles. Cario University emerged as the top research institution. The United States led in terms of article publications with a count of 276. In the past 5 years, the research trends in this field have primarily focused on tranexamic acid and epidermal melasma, as indicated by the burst analysis of publications and keywords. CONCLUSIONS: The United States continues to lead in terms of institutions and research output. The current emphasis is on the meticulous implementation of tranexamic acid and laser therapy. It is crucial to foster enhanced collaboration among countries, institutions, and authors to facilitate improved research.
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BACKGROUND: The study aims to evaluate the outcomes of metastasis-directed stereotactic body radiation therapy (SBRT) in metastatic nasopharyngeal carcinoma (mNPC). METHODS: We reviewed all SBRT conducted in patients with mNPC in our institution between 2013 and 2022. Systemic therapy was performed with chemotherapy with or without anti-programmed death-1 (PD-1) therapy. Local treatment delivered with ablative purpose in stereotactic setting with dose/fraction ≥5 Gy was evaluated. Kaplan-Meier analyses were used to determine the rates of local control (LC), progression-free survival (PFS), and overall survival (OS). Univariate and multivariate analyses were performed by Cox regression. RESULTS: A total of 54 patients with 76 metastatic sites receiving SBRT were analyzed. Median follow-up was 49 months. The 3-year LC, PFS, and OS rates were 89.1%, 29.4%, and 57.9%, respectively. Adding a PD-1 inhibitor to SBRT tended to prolong median OS (50.1 vs. 32.2 months, p = 0.068). Patients receiving a biological effective dose (BED, α/ß = 10) ≥ 80 Gy had a significantly longer median OS compared to those who received a lower dose (not reached vs. 29.5 months, p = 0.004). Patients with oligometastases (1-5 metastases) had a better median OS (not reached vs. 29.5 months, p < 0.001) and PFS (34.3 vs. 4.6 months, p < 0.001). Pretreatment EBV-DNA and maintenance therapy were also significant predictors for OS. CONCLUSIONS: Metastatic NPC patients could benefit from metastases-directed SBRT in combination with systemic therapy.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Radiocirugia , Humanos , Radiocirugia/métodos , Masculino , Femenino , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/terapia , Persona de Mediana Edad , Adulto , Anciano , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/terapia , Estudios Retrospectivos , Resultado del Tratamiento , Metástasis de la Neoplasia , Adulto Joven , Supervivencia sin Progresión , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estimación de Kaplan-MeierRESUMEN
Exosomes, small extracellular vesicles derived from cells, are known to carry important bioactive molecules such as proteins, nucleic acids, and lipids. These bioactive components play crucial roles in cell signaling, immune response, and tumor metastasis, making exosomes potential diagnostic biomarkers for various diseases. However, current methods for detecting tumor exosomes face scientific challenges including low sensitivity, poor specificity, complicated procedures, and high costs. It is essential to surmount these obstacles to enhance the precision and dependability of diagnostics that rely on exosomes. Merging DNA signal amplification techniques with the signal boosting capabilities of nanomaterials presents an encouraging strategy to overcome these constraints and improve exosome detection. This article highlights the use of DNA signal amplification technology and nanomaterials' signal enhancement effect to improve the detection of exosomes. This review seeks to offer valuable perspectives for the enhancement of amplification methods applied in practical cancer diagnosis and prognosis by providing an overview of how these novel technologies are utilized in exosome-based diagnostic procedures.
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Exosomas , Vesículas Extracelulares , Neoplasias , Humanos , Neoplasias/diagnóstico , Biomarcadores , ADNRESUMEN
Secondary lung injury after SCI is a major cause of patient mortality, with apoptosis playing a key role. This study aimed to explore the impact of treadmill training and miR145-5p on the MAPK/Erk signaling pathway and apoptosis in rats with complete SCI. SD rats were used to establish T10 segmental complete SCI models and underwent treadmill training 3, 7, or 14 days postinjury. Various techniques including arterial blood gas analysis, lung wet/dry weight ratio, HE staining, immunofluorescence staining, immunohistochemical staining, qRT-PCR, and Western blotting were employed to assess alterations in lung function and the expression levels of crucial apoptosis-related factors. In order to elucidate the specific mechanism, the impact of miR145-5p on the MAPK/Erk pathway and its role in apoptosis in lung cells were confirmed through miR145-5p overexpression and knockdown experiments. Following spinal cord injury (SCI), an increase in apoptosis, activation of the MAPK/Erk pathway, and impairment of lung function were observed in SCI rats. Conversely, treadmill training resulted in a reduction in alveolar cell apoptosis, suppression of the MAPK/Erk pathway, and enhancement of lung function. The gene MAP3K3 was identified as a target of miR145-5p. The influence of miR145-5p on the MAPK/Erk pathway and its impact on apoptosis in alveolar cells were confirmed through the manipulation of miR145-5p expression levels. The upregulation of miR145-5p in spinal cord injury (SCI) rats led to a reduction in MAP3K3 protein expression within lung tissues, thereby inhibiting the MAPK/Erk signaling pathway and decreasing apoptosis. Contrarily, rats with miR145-5p knockdown undergoing treadmill training exhibited an increase in miR145-5p expression levels, resulting in the inhibition of MAP3K3 protein expression in lung tissues, suppression of the MAPK/Erk pathway, and mitigation of lung cell apoptosis. Ultimately, the findings suggest that treadmill training may attenuate apoptosis in lung cells post-spinal cord injury by modulating the MAP3K3 protein through miR145-5p to regulate the MAPK/Erk signaling pathway.
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Apoptosis , Sistema de Señalización de MAP Quinasas , MicroARNs , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/terapia , Ratas , MicroARNs/genética , MicroARNs/metabolismo , Masculino , Pulmón/metabolismo , Pulmón/patología , Pulmón/fisiopatología , Células Epiteliales Alveolares/metabolismo , Modelos Animales de EnfermedadRESUMEN
The discovery of upstream regulatory genes of a gene of interest still remains challenging. Here we applied a scalable computational method to unbiasedly predict candidate regulatory genes of critical transcription factors by searching the whole genome. We illustrated our approach with a case study on the master regulator FOXP3 of human primary regulatory T cells (Tregs). While target genes of FOXP3 have been identified, its upstream regulatory machinery still remains elusive. Our methodology selected five top-ranked candidates that were tested via proof-of-concept experiments. Following knockdown, three out of five candidates showed significant effects on the mRNA expression of FOXP3 across multiple donors. This provides insights into the regulatory mechanisms modulating FOXP3 transcriptional expression in Tregs. Overall, at the genome level this represents a high level of accuracy in predicting upstream regulatory genes of key genes of interest.
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Factores de Transcripción Forkhead , Linfocitos T Reguladores , Transcriptoma , Humanos , Factores de Transcripción Forkhead/genética , Linfocitos T Reguladores/inmunología , Transcriptoma/genética , Biología Computacional/métodos , Regulación de la Expresión Génica/genética , Perfilación de la Expresión Génica/métodos , Genes Reguladores/genéticaRESUMEN
Background: Psoriasis is a chronic, inflammatory skin disease with autoimmune characteristics. Recent research has made significant progress in the field of psoriasis metabolomics. However, there is a lack of bibliometric analysis on metabolomics of psoriasis. The objective of this study is to utilize bibliometrics to present a comprehensive understanding of the knowledge structure and research hotspots in psoriasis within the field of metabolomics. Methods: We conducted a bibliometric analysis by searching the Web of Science Core Collection database for publications on metabolomics in psoriasis from 2011 to 2024. To perform this analysis, we utilized tools such as VOSviewers, CiteSpace, and the R package "bibliometrix". Results: A total of 307 articles from 47 countries, with the United States and China leading the way, were included in the analysis. The publications focusing on metabolomics in psoriasis have shown a steady year-on-year growth. The Medical University of Bialystok is the main research institution. The International Journal of Molecular Sciences emerges as the prominent journal in the field, while the Journal of Investigative Dermatology stands out as the highly co-cited publication. A total of 2029 authors contributed to these publications, with Skrzydlewska Elzbieta, Baran Anna, Flisiak Iwona, Murakami Makoto being the most prolific contributors. Notably, Armstrong April W. received the highest co-citation. Investigating the mechanisms of metabolomics in the onset and progression of psoriasis, as well as exploring therapeutic strategies, represents the primary focus of this research area. Emerging research hotspots encompass inflammation, lipid metabolism, biomarker, metabolic syndrome, obesity, and arthritis. Conclusion: The results of this study indicate that metabolism-related research is thriving in psoriasis, with a focus on the investigation of metabolic targets and interventions within the metabolic processes. Metabolism is expected to be a hot topic in future psoriasis research.