RESUMEN
BACKGROUND: Innate/adaptive immunity is the key to anti-tumor therapy. However, its causal relationship to Gastrointestinal (GI) cancer remains unclear. METHODS: Immunity genes were extracted from the MSigDB database. The Genome-wide association studies (GWAS) summary data of GI cancer were integrated with expression quantitative trait loci (eQTL) and DNA methylation quantitative trait loci (mQTL) associated with genes. Summary-data-based Mendelian randomization (SMR) and co-localization analysis were used to reveal causal relationships between genes and GI cancer. Two-sample MR analysis was used for sensitivity analysis. Single cell analysis clarified the enrichment of genes. RESULTS: Three-step SMR analysis showed that a putative mechanism, cg17294865 CpG site regulating HLA-DRA expression was negatively associated with gastric cancer risk. HLA-DRA was significantly differentially expressed in monocyte/macrophage and myeloid cells in gastric cancer. CONCLUSION: This study provides evidence that upregulating the expression level of HLA-DRA can reduce the risk of gastric cancer.
Asunto(s)
Inmunidad Adaptativa , Metilación de ADN , Neoplasias Gastrointestinales , Estudio de Asociación del Genoma Completo , Inmunidad Innata , Análisis de la Aleatorización Mendeliana , Sitios de Carácter Cuantitativo , Humanos , Inmunidad Innata/genética , Inmunidad Adaptativa/genética , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/inmunología , Neoplasias Gástricas/genética , Neoplasias Gástricas/inmunología , Cadenas alfa de HLA-DR/genética , Islas de CpG/genética , MultiómicaRESUMEN
Rheumatoid arthritis (RA) is an autoimmune disease causing progressive joint damage. Early diagnosis and treatment is critical, but remains challenging due to RA complexity and heterogeneity. Machine learning (ML) techniques may enhance RA management by identifying patterns within multidimensional biomedical data to improve classification, diagnosis, and treatment predictions. In this review, we summarize the applications of ML for RA management. Emerging studies or applications have developed diagnostic and predictive models for RA that utilize a variety of data modalities, including electronic health records, imaging, and multi-omics data. High-performance supervised learning models have demonstrated an Area Under the Curve (AUC) exceeding 0.85, which is used for identifying RA patients and predicting treatment responses. Unsupervised learning has revealed potential RA subtypes. Ongoing research is integrating multimodal data with deep learning to further improve performance. However, key challenges remain regarding model overfitting, generalizability, validation in clinical settings, and interpretability. Small sample sizes and lack of diverse population testing risks overestimating model performance. Prospective studies evaluating real-world clinical utility are lacking. Enhancing model interpretability is critical for clinician acceptance. In summary, while ML shows promise for transforming RA management through earlier diagnosis and optimized treatment, larger scale multisite data, prospective clinical validation of interpretable models, and testing across diverse populations is still needed. As these gaps are addressed, ML may pave the way towards precision medicine in RA.
Asunto(s)
Artritis Reumatoide , Aprendizaje Automático , Medicina de Precisión , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/terapia , Humanos , Medicina de Precisión/métodos , Reumatología/métodos , Manejo de la EnfermedadRESUMEN
Objective: To quantitatively compare the diagnostic value of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) in solid pancreatic mass lesions using a systematic evaluation method.Methods: A systematic literature search was conducted on public databases to include studies comparing the diagnostic value of EUS-FNA and EUS-FNB in solid pancreatic mass lesions. The combined effect size was estimated using mean difference (MD) and risk difference (RD) respectively, and the corresponding 95% confidence interval (CI) was calculated.Results: The 12 articles (7 RCTs and 5 cohort studies) met the inclusion criteria of this study. The meta-analysis showed that compared with EUS-FNB, EUS-FNA had lower diagnostic accuracy (RD: -0.08, 95% CI: -0.15, -0.01) and specimen adequacy (RD: -0.08, 95% CI: -0.15, -0.02), while higher required number of needle passes (MD: 0.42, 95% CI: 0.12, 0.73). However, EUS-FNB and EUS-FNA presented similar overall complications (RD: 0.00, 95% CI: -0.01, 0.02) and technical failures (RD: -0.01, 95% CI: -0.02, 0.00), without statistically significant differences.Conclusions: Compared with EUS-FNA, EUS-FNB seems to be a better choice for diagnosing suspected pancreatic lesions.
Asunto(s)
Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Páncreas , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico , Páncreas/patología , Páncreas/diagnóstico por imagen , Estudios Prospectivos , Endosonografía/métodosRESUMEN
Psoriasis is a chronic inflammatory skin disease characterized by the excessive proliferation of keratinocytes and heightened immune activation. Targeting pathogenic genes through small interfering RNA (siRNA) therapy represents a promising strategy for the treatment of psoriasis. This mini-review provides a comprehensive summary of siRNA research targeting the pathogenesis of psoriasis, covering aspects such as keratinocyte function, inflammatory cell roles, preclinical animal studies, and siRNA delivery mechanisms. It details recent advancements in RNA interference that modulate key factors including keratinocyte proliferation (Fibroblast Growth Factor Receptor 2, FGFR2), apoptosis (Interferon Alpha Inducible Protein 6, G1P3), differentiation (Grainyhead Like Transcription Factor 2, GRHL2), and angiogenesis (Vascular Endothelial Growth Factor, VEGF); immune cell infiltration and inflammation (Tumor Necrosis Factor-Alpha, TNF-α; Interleukin-17, IL-17); and signaling pathways (JAK-STAT, Nuclear Factor Kappa B, NF-κB) that govern immunopathology. Despite significant advances in siRNA-targeted treatments for psoriasis, several challenges persist. Continued scientific developments promise the creation of more effective and safer siRNA medications, potentially enhancing the quality of life for psoriasis patients and revolutionizing treatments for other diseases. This article focuses on the most recent research advancements in targeting the pathogenesis of psoriasis with siRNA and explores its future therapeutic prospects.
RESUMEN
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Macrophages are key effector cells that play a central role in RA pathogenesis through their ability to polarize into distinct functional phenotypes. An imbalance favoring pro-inflammatory M1 macrophages over anti-inflammatory M2 macrophages disrupts immune homeostasis and exacerbates joint inflammation. Multiple signaling pathways, including Notch, JAK/STAT, NF-κb, and MAPK, regulate macrophage polarization towards the M1 phenotype in RA. Metabolic reprogramming also contributes to this process, with M1 macrophages prioritizing glycolysis while M2 macrophages utilize oxidative phosphorylation. Redressing this imbalance by modulating macrophage polarization and metabolic state represents a promising therapeutic strategy. Furthermore, complex bidirectional interactions exist between synovial macrophages and fibroblast-like synoviocytes (FLS), forming a self-perpetuating inflammatory loop. Macrophage-derived factors promote aggressive phenotypes in FLS, while FLS-secreted mediators contribute to aberrant macrophage activation. Elucidating the signaling networks governing macrophage polarization, metabolic adaptations, and crosstalk with FLS is crucial to developing targeted therapies that can restore immune homeostasis and mitigate joint pathology in RA.
Asunto(s)
Artritis Reumatoide , Fibroblastos , Activación de Macrófagos , Macrófagos , Transducción de Señal , Membrana Sinovial , Humanos , Artritis Reumatoide/metabolismo , Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Macrófagos/inmunología , Macrófagos/metabolismo , Membrana Sinovial/metabolismo , Membrana Sinovial/inmunología , Membrana Sinovial/patología , Fibroblastos/metabolismo , Fibroblastos/inmunología , Animales , Activación de Macrófagos/inmunología , Comunicación Celular/inmunología , Reprogramación MetabólicaRESUMEN
OBJECTIVES: To observe the effect of electro-scalp acupuncture (ESA) on the expression of cytochrome P450a1/b1 (CYP27a1/b1), cytochrome P45024a (CYP24a), signal transducer and activator of transcription (STAT)4, STAT6, tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-4 in ischemic cerebral cortex of rats with acute ischemic stroke, so as to explore its mechanism in alleviating inflammatory reaction of ischemic stroke. METHODS: Sixty SD rats were randomly divided into sham-operation, model, vitamin D3 and ESA groups, with 15 rats in each group. The middle cerebral artery occlusion rat model was established with thread ligation according to Zea-Longa's method. Rats in the vitamin D3 group were given 1, 25-VitD3 solution (3 ng·100 g-1·d-1) by gavage, once daily for 7 days. Rats in the ESA group were treated at bilateral anterior parietotemporal slash (MS6) with ESA (2 Hz/100 Hz, 1 mA), 30 min a day for 7 days. Before and after interventions, the neurological deficit score and neurobehavioral score were evaluated. TTC staining was used to detect the volume of cerebral infarction in rats. The positive expressions of CYP24a, CYP27a1 and CYP27b1 in the cerebral cortex of ischemic area were detected by immunofluorescence. The mRNA expressions of STAT4 and STAT6 in the cerebral cortex of ischemic area were detected by quantitative real-time PCR. The protein expression levels of TNF-α, IL-1ß and IL-4 in the cerebral cortex of ischemic area were detected by Western blot. RESULTS: Compared with the sham-operation group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1ß in cerebral cortex were increased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA, protein expression level of IL-4 were decreased (P<0.01) in the model group. After the treatment and compared with the model group, the neurological deficit score, neurobehavioral score, the percentage of cerebral infarction volume, the positive expression level of CYP24a and mRNA expression level of STAT4, protein expression levels of TNF-α and IL-1ß in cerebral cortex were decreased (P<0.01), while the positive expression levels of CYP27a1/b1 and STAT6 mRNA expression level, protein expression level of IL-4 were increased (P<0.01) in the ESA and vitamin D3 groups. CONCLUSIONS: ESA can alleviate the inflammatory response in ischemic stroke, which maybe related to its function in regulating the balance between CYP27a1/b1 and CYP24a, converting vitamin D into active vitamin D3, inhibiting vitamin D3 degradation, and regulating Th1/Th2 balance.
Asunto(s)
Infarto de la Arteria Cerebral Media , Vitamina D3 24-Hidroxilasa , Animales , Humanos , Masculino , Ratas , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/metabolismo , Puntos de Acupuntura , Isquemia Encefálica/terapia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/genética , Corteza Cerebral/metabolismo , Colestanotriol 26-Monooxigenasa/genética , Colestanotriol 26-Monooxigenasa/metabolismo , Citocinas/metabolismo , Citocinas/genética , Electroacupuntura , Infarto de la Arteria Cerebral Media/terapia , Infarto de la Arteria Cerebral Media/genética , Infarto de la Arteria Cerebral Media/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Vitamina D3 24-Hidroxilasa/genética , Vitamina D3 24-Hidroxilasa/metabolismoRESUMEN
An innovative method for the fabrication of a catalyst-sensitizer dyad-based photoelectrode was developed by using the coordinated interaction between the pyridine-2,6-dicarboxylic group and Sn4+. A dyad (C1 + PDI) was loaded on the mesoporous BiFeO3 (BFO) photocathode for light-driven H2 generation. The dyad could expand the light absorption range and promote the surface charge separation of BFO, resulting in an enhanced photocurrent.
RESUMEN
INTRODUCTION: Neonatal respiratory failure (NRF) is a serious condition that often has high mortality and morbidity, effective interventions can be delivered in the future by identifying the risk factors associated with morbidity and mortality. However, recent advances in respiratory support have improved neonatal intensive care units (NICUs) care in China. We aimed to provide an updated review of the clinical profile and outcomes of NRF in the Jiangsu province. METHODS: Infants treated for NRF in the NICUs of 28 hospitals between March 2019 and March 2022 were retrospectively reviewed. Data collected included baseline perinatal and neonatal parameters, NICU admission- and treatment-related data, and patient outcomes in terms of mortality, major morbidity, and survival without major morbidities. RESULTS: A total of 5548 infants with NRF were included in the study. The most common primary respiratory disorder was respiratory distress syndrome (78.5%). NRF was managed with non-invasive and invasive respiratory support in 59.8% and 14.5% of patients, respectively. The application rate of surfactant therapy was 38.5%, while that of neonatal extracorporeal membrane oxygenation therapy was 0.2%. Mortality and major morbidity rates of 8.5% and 23.2% were observed, respectively. Congenital anomalies, hypoxic-ischemic encephalopathy, invasive respiratory support only and inhaled nitric oxide therapy were found to be significantly associated with the risk of death. Among surviving infants born at < 32 weeks of gestation or with a birth weight < 1500 g, caffeine therapy and repeat mechanical ventilation were demonstrated to significantly associate with increased major morbidity risk. CONCLUSION: Our study demonstrates the current clinical landscape of infants with NRF treated in the NICU, and, by proxy, highlights the ongoing advancements in the field of perinatal and neonatal intensive care in China.
Asunto(s)
Unidades de Cuidado Intensivo Neonatal , Síndrome de Dificultad Respiratoria del Recién Nacido , Humanos , Recién Nacido , China/epidemiología , Estudios Retrospectivos , Femenino , Masculino , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Insuficiencia Respiratoria/terapia , Surfactantes Pulmonares/uso terapéutico , Surfactantes Pulmonares/administración & dosificación , Oxigenación por Membrana Extracorpórea , Respiración Artificial/estadística & datos numéricos , Resultado del TratamientoRESUMEN
Impaired long-term memory, a complication of traumatic stress including hemorrhage shock and resuscitation (HSR), has been reported to be associated with multiple neurodegenerations. The ventral tegmental area (VTA) participates in both learned appetitive and aversive behaviors. In addition to being prospective targets for the therapy of addiction, depression, and other stress-related diseases, VTA glutamatergic neurons are becoming more widely acknowledged as powerful regulators of reward and aversion. This study revealed that HSR exposure induces memory impairments and decreases the activation in glutamatergic neurons, and decreased ß power in the VTA. We also found that optogenetic activation of glutamatergic neurons in the VTA mitigated HSR-induced memory impairments, and restored ß power. Moreover, hydrogen sulfide (H2S), a gasotransmitter with pleiotropic roles, has neuroprotective functions at physiological concentrations. In vivo, H2S administration improved HSR-induced memory deficits, elevated c-fos-positive vesicular glutamate transporters (Vglut2) neurons, increased ß power, and restored the balance of γ-aminobutyric acid (GABA) and glutamate in the VTA. This work suggests that glutamatergic neuron stimulation via optogenetic assay and exogenous H2S may be useful therapeutic approaches for improving memory deficits following HSR.
Asunto(s)
Modelos Animales de Enfermedad , Ácido Glutámico , Sulfuro de Hidrógeno , Trastornos de la Memoria , Ratones Endogámicos C57BL , Neuronas , Animales , Sulfuro de Hidrógeno/farmacología , Sulfuro de Hidrógeno/uso terapéutico , Ratones , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/etiología , Trastornos de la Memoria/terapia , Masculino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ácido Glutámico/metabolismo , Ácido Glutámico/toxicidad , Choque Hemorrágico , Área Tegmental Ventral/efectos de los fármacos , Área Tegmental Ventral/metabolismo , Optogenética/métodosRESUMEN
BACKGROUND: The Menstrual Distress Questionnaire (MDQ) is a commonly used questionnaire that assesses various symptoms and distress associated with the menstrual cycle in women. However, the questionnaire has not been completely translated into Chinese with rigorous reliability and validity testing. METHODS: This study translated the Menstrual Distress Questionnaire Form Cycle (MDQC) from English into Chinese: MDQCC in two stages. First, it was translated forward and backward using Jones' model; second, to test the validity and reliability, 210 Chinese-speaking women were recruited through online announcements and posters posted between June 2019 and May 2020. Expert validity, construct validity, convergent validity, and factorial validity were determined using content validity index (CVI), intraclass correlation coefficient (ICC), composite reliability (CR), and exploratory factor analysis, respectively. For concurrent criterion validity, MDQCC score was compared with three existing pain scales. Reliability was evaluated using internal consistency across items and two-week test-retest reliability over time. RESULTS: The CVI for content validity was .92. Item-CVI for expert validities among the 46 items ranged from .50 - 1; scale-CVI for the eight subscales, from .87 - 1; ICC, from .650 - .897; and CRs, from .303 - .881. Pearson correlation coefficients between MDQCC and short-form McGill pain questionnaire, present pain intensity, and visual analog scale scores were .640, .519, and .575, respectively. Cronbach's α for internal consistency was satisfactory (.932). ICC for test-retest reliability was .852 for the entire MDQCC. CONCLUSION: MDQCC was valid and reliable for Mandarin Chinese-speaking women. It can be used to evaluate female psychiatric symptoms related to the menstrual cycle in future work.
The Menstrual Distress Questionnaire has been used to evaluate menstrual distress, including dysmenorrhoea and premenstrual syndrome. This questionnaire has been translated into Persian, Korean, Japanese, and Cantonese, rendering it to be used more and more widely all over the world. The study translated all 46 items of the Menstrual Distress Questionnaire from English to Mandarin Chinese using a two-stage strategy. The Chinese version of this questionnaire developed by the present study was found to be a valid and reliable tool in Chinese Mandarin-speaking female populations. It could be used to evaluate women's physical and psychiatric symptoms related to the menstrual cycle in future works.
Asunto(s)
Pueblo Asiatico , Ciclo Menstrual , Femenino , Humanos , Correlación de Datos , Análisis Factorial , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVES: Rheumatoid arthritis (RA) is a complex disease with a challenging diagnosis, especially in seronegative patients. The aim of this study is to investigate whether the methylation sites associated with the overall immune response in RA can assist in clinical diagnosis, using targeted methylation sequencing technology on peripheral venous blood samples. METHODS: The study enrolled 241 RA patients, 30 osteoarthritis patients (OA), and 30 healthy volunteers control (HC). Fifty significant cytosine guanine (CG) sites between undifferentiated arthritis and RA were selected and analyzed using targeted DNA methylation sequencing. Logistic regression models were used to establish diagnostic models for different clinical features of RA, and six machine learning methods (logit model, random forest, support vector machine, adaboost, naive bayes, and learning vector quantization) were used to construct clinical diagnostic models for different subtypes of RA. Least absolute shrinkage and selection operator regression and detrended correspondence analysis were utilized to screen for important CGs. Spearman correlation was used to calculate the correlation coefficient. RESULTS: The study identified 16 important CG sites, including tumor necrosis factort receptor associated factor 5 (TRAF5) (chr1:211500151), mothers against decapentaplegic homolog 3 (SMAD3) (chr15:67357339), tumor endothelial marker 1 (CD248) (chr11:66083766), lysosomal trafficking regulator (LYST) (chr1:235998714), PR domain zinc finger protein 16 (PRDM16) (chr1:3307069), A-kinase anchoring protein 10 (AKAP10) (chr17:19850460), G protein subunit gamma 7 (GNG7) (chr19:2546620), yes1 associated transcriptional regulator (YAP1) (chr11:101980632), PRDM16 (chr1:3163969), histone deacetylase complex subunit sin3a (SIN3A) (chr15:75747445), prenylated rab acceptor protein 2 (ARL6IP5) (chr3:69134502), mitogen-activated protein kinase kinase kinase 4 (MAP3K4) (chr6:161412392), wnt family member 7A (WNT7A) (chr3:13895991), inhibin subunit beta B (INHBB) (chr2:121107018), deoxyribonucleic acid replication helicase/nuclease 2 (DNA2) (chr10:70231628) and chromosome 14 open reading frame 180 (C14orf180) (chr14:105055171). Seven CG sites showed abnormal changes between the three groups (P < 0.05), and 16 CG sites were significantly correlated with common clinical indicators (P < 0.05). Diagnostic models constructed using different CG sites had an area under the receiver operating characteristic curve (AUC) range of 0.64-0.78 for high-level clinical indicators of high clinical value, with specificity ranging from 0.42 to 0.77 and sensitivity ranging from 0.57 to 0.88. The AUC range for low-level clinical indicators of high clinical value was 0.63-0.72, with specificity ranging from 0.48 to 0.74 and sensitivity ranging from 0.72 to 0.88. Diagnostic models constructed using different CG sites showed good overall diagnostic accuracy for the four subtypes of RA, with an accuracy range of 0.61-0.96, a balanced accuracy range of 0.46-0.94, and an AUC range of 0.46-0.94. CONCLUSIONS: This study identified potential clinical diagnostic biomarkers for RA and provided novel insights into the diagnosis and subtyping of RA. The use of targeted deoxyribonucleic acid (DNA) methylation sequencing and machine learning methods for establishing diagnostic models for different clinical features and subtypes of RA is innovative and can improve the accuracy and efficiency of RA diagnosis.
Asunto(s)
Artritis Reumatoide , Neoplasias , Osteoartritis , Femenino , Humanos , Metilación de ADN , Teorema de Bayes , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/genética , Osteoartritis/diagnóstico , Osteoartritis/genética , Biomarcadores , ADN , Neoplasias/genética , Antígenos de Neoplasias , Antígenos CDRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection caused the COVID-19 pandemic, impacting the global economy and medical system due to its fast spread and extremely high infectivity. Efficient control of the spread of the disease relies on a fast, accurate, and convenient detection system for the early screening of the infected population. Although reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is the gold-standard method for SARS-CoV-2 RNA analysis, it has complex experimental procedures and relies on expensive instruments and professional operators. In this work, we proposed a simple, direct, amplification-free lateral flow immunoassay (LFIA) with dual-mode detection of SARS-CoV-2 RNA via direct visualization as well as fluorescence detection. The viral RNA was detected by the designed DNA probes to specifically hybridize with the conserved open reading frame 1ab (ORF1ab), envelope protein (E), and nucleocapsid (N) regions of the SARS-CoV-2 genome to form DNA-RNA hybrids. These hybrids were then recognized by the dual-mode gold nanoparticles (DMNPs) to produce two different readout signals. The fluorescence characteristics of different sizes of GNPs were explored. Under the optimized conditions, the LFIA presented a linear detection range of 104-106 TU/mL with a limit of detection (LOD) of 0.76, 1.83, and 2.58 × 104 TU/mL for lentiviral particles carrying SARS-CoV-2 ORF1ab, E, and N motifs, respectively, in the fluorescent mode, which was up to 10 times more sensitive than the colorimetric mode. Furthermore, the LFIA exhibited excellent specificity to SARS-CoV-2 in comparison with other respiratory viruses. It could be used to detect SARS-CoV-2 in saliva samples. The developed LFIA represents a promising and convenient point-of-care method for dual-mode, rapid detection of SARS-CoV-2, especially in the periods with high infectivity.
RESUMEN
The Euodia genus comprises numerous untapped medicinal plants that warrant thorough evaluation for their potential as valuable natural sources of herbal medicine or food flavorings. In this study, untargeted metabolomics and in vitro functional methods were employed to analyze fruit extracts from 11 significant species of the Euodia genus. An investigation of the distribution of metabolites (quinolone and indole quinazoline alkaloids) in these species indicated that E. rutaecarpa (Euodia rutaecarpa) was the most widely distributed species, followed by E. compacta (Euodia compacta), E. glabrifolia (Euodia glabrifolia), E. austrosinensis (Euodia austrosinensis), and E. fargesii (Euodia fargesii). There have been reports on the close correlation between indole quinazoline alkaloids and their anti-tumor activity, especially in E. rutaecarpa fruits which exhibit effectiveness against various types of cancer, such as SGC-7901, Hela, A549, and other cancer cell lines. Additionally, the E. rutaecarpa plant contains indole quinazoline alkaloids, which possess remarkable antibacterial properties. Our results offer novel insights into the utilization of Euodia resources in the pharmaceutical industry.
Asunto(s)
Alcaloides , Evodia , Plantas Medicinales , Quinolonas , Rutaceae , Humanos , Extractos Vegetales , Alcaloides Indólicos , Células HeLa , QuinazolinasRESUMEN
Blood vessels are essential for bone development and metabolism. Type H vessels in bone, named after their high expression of CD31 and Endomucin (Emcn), have recently been reported to locate mainly in the metaphysis, exhibit different molecular properties and couple osteogenesis and angiogenesis. A strong correlation between type H vessels and bone metabolism is now well-recognized. The crosstalk between type H vessels and osteoprogenitor cells is also involved in bone metabolism-related diseases such as osteoporosis, osteoarthritis, fracture healing and bone defects. Targeting the type H vessel formation may become a new approach for managing a variety of bone diseases. This review highlighted the roles of type H vessels in bone-related diseases and summarized the research attempts to develop targeted intervention, which will help us gain a better understanding of their potential value in clinical application.
Asunto(s)
Enfermedades Óseas Metabólicas , Osteoporosis , Humanos , Osteogénesis/genética , Huesos/metabolismo , Osteoporosis/metabolismo , Curación de Fractura , Neovascularización FisiológicaRESUMEN
During the utilization of lignocellulosic biomass such as corn stover, many by-products are produced in the pretreatment process that can severely inhibit the activity of microbes in the fermentation step. To achieve efficient biomass conversion, detoxification is usually required before microbial fermentation. In this study, the prehydrolysate from dilute acid pretreatment of corn stover was used as a lactic acid fermentation substrate. Biochars made from corn stover (CSB), cow manure (CMB), and a mixture of corn stover and cow manure (MB) were applied for the detoxification of the prehydrolysate. All three types of biochar had a porous structure with a specific surface area ranging from 4.08 m2 g-1 (CMB) to 7.03 m2 g-1 (MB). After detoxification, both the numbers of inhibitors and their concentrations in the prehydrolysate decreased, indicating that the biochars prepared in this study were effective in inhibitor removal. The concentration of lactic acid obtained from the prehydrolysate without detoxification was only 12.43 g L-1 after fermentation for 96 h with a productivity of 0.13 g (L h)-1. Although the specific area of CMB was the lowest among the three biochars, the CMB-treated prehydrolysate resulted in the highest lactic acid concentration of 39.25 g L-1 at 96 h with a productivity of 0.41 g (L h)-1. The lactic acid bacteria in the CMB-treated prehydrolysate grew faster than the other two biochars, reaching an OD value of 8.12 at 48 h. The results showed promise for the use of agricultural wastes to make biochar to increase the yield of lactic acid fermentation through the detoxification process.
RESUMEN
Aims: Myocardial ischemia can affect traditional right ventricular (RV) pacing parameters, but it is unclear whether coronary artery disease (CAD) impact the pacing parameters and electrophysiological characteristics of left bundle branch area pacing (LBBaP) as a physiological pacing representative. Methods: Patients who underwent coronary angiography (CAG) after/before the LBBaP procedure and underwent percutaneous coronary intervention after LBBaP procedure were divided into CAD group and Non-CAD group according to visual CAG. Pacing parameters and electrophysiological characteristics were recorded at LBBaP implantation. Multivariate logistic regression analysis was implemented to evaluate the association between CAD and higher capture threshold. Sensitivity analyses were conducted to verify result stability. Results: A total of 176 patients met inclusion criteria (115 Non-CAD patients and 61 CAD patients) with a mean age of 71.1 ± 9.0 years. Compared with the Non-CAD patients, CAD patients had the higher capture threshold (0.67 ± 0.22 V vs. 0.82 ± 0.28 V, P < 0.001) and lower R-wave amplitude (12.5 ± 4.8 mV vs. 10.1 ± 2.7 mV, P = 0.001). Moreover, CAD was independently associated with higher capture threshold (adjusted Odds ratio (OR) 3.418, 95% confidence interval (CI): 1.621-7.206, P = 0.001), which was further validated through sensitivity analyses. Conclusion: Patients without CAD might have safer pacing parameters in the LBBaP procedure. Besides, CAD might be the risk factor of capture threshold increase during permanent LBBaP implantation.
RESUMEN
NonlinearI-Vcharacteristics associated with Coulomb blockade (CB) in conducting polymers were systematically investigated. At low temperatures, a crossover from Ohmic to nonlinear behavior was observed, along with drastically enhanced noise in differential conductance right from the crossover. The fluctuation can be well explained by the Coulombic oscillation in the collective percolation system, where the charge transport is related to the Coulombic charging energy between crystalline domains. Furthermore, a distinct quantum conductance, the fingerprint of CB caused by the individual tunneling between crystalline grains, was observed in sub-100 nm devices, confirming a strong association between nonlinearI-Vcharacteristics and CB effect.
RESUMEN
Tubulin beta 4A class IVa (TUBB4A) spectrum disorders include autosomal dominant dystonia type 4 or hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC syndrome). However, in rare cases, only mild hypomyelination in the cortex with no basal ganglia atrophy may be observed. We report a case of a family with TUBB4A mutation and complicated hereditary spasticity paraplegia (HSP). We performed quadro whole-exome sequencing (WES) on the family to identify the causative gene of progressive spastic paraparesis with isolated hypomyelination leukodystrophy. We identified a novel TUBB4A p.F341L mutation, which was present in all three affected patients but absent in the unaffected father. The affected patients presented with adult-onset TUBB4A disorder, predominant spastic paraparesis with/without ataxia, and brain hypomyelination with no cognitive impairment or extrapyramidal symptoms. In the literature, HSP is considered a TUBB4A spectrum disorder.
RESUMEN
Objective: To investigate the potential association between Anoikis-related genes, which are responsible for preventing abnormal cellular proliferation, and rheumatoid arthritis (RA). Methods: Datasets GSE89408, GSE198520, and GSE97165 were obtained from the GEO with 282 RA patients and 28 healthy controls. We performed differential analysis of all genes and HLA genes. We performed a protein-protein interaction network analysis and identified hub genes based on STRING and cytoscape. Consistent clustering was performed with subgrouping of the disease. SsGSEA were used to calculate immune cell infiltration. Spearman's correlation analysis was employed to identify correlations. Enrichment scores of the GO and KEGG were calculated with the ssGSEA algorithm. The WGCNA and the DGIdb database were used to mine hub genes' interactions with drugs. Results: There were 26 differentially expressed Anoikis-related genes (FDR = 0.05, log2FC = 1) and HLA genes exhibited differential expression (P < 0.05) between the disease and control groups. Protein-protein interaction was observed among differentially expressed genes, and the correlation between PIM2 and RAC2 was found to be the highest; There were significant differences in the degree of immune cell infiltration between most of the immune cell types in the disease group and normal controls (P < 0.05). Anoikis-related genes were highly correlated with HLA genes. Based on the expression of Anoikis-related genes, RA patients were divided into two disease subtypes (cluster1 and cluster2). There were 59 differentially expressed Anoikis-related genes found, which exhibited significant differences in functional enrichment, immune cell infiltration degree, and HLA gene expression (P < 0.05). Cluster2 had significantly higher levels in all aspects than cluster1 did. The co-expression network analysis showed that cluster1 had 51 hub differentially expressed genes and cluster2 had 72 hub differentially expressed genes. Among them, three hub genes of cluster1 were interconnected with 187 drugs, and five hub genes of cluster2 were interconnected with 57 drugs. Conclusion: Our study identified a link between Anoikis-related genes and RA, and two distinct subtypes of RA were determined based on Anoikis-related gene expression. Notably, cluster2 may represent a more severe state of RA.