RESUMEN

Small pentacyclic peptides, represented by nisin, have been successfully utilized as preservatives in the food industry and have evolved into a paradigm for understanding the genetic structure, expression, and control of genes created by lantibiotics. Due to the ever-increasing antibiotic resistance, nisin-relevant antimicrobial peptides have received much attention, which calls for a summarization of their synthesis, modification and applications. In this review, we first provided a timeline of select highlights in nisin biosynthesis and engineering. Then, we outlined the current developments in nisin synthesis. We also provided an overview of the engineering, screening, and production of nisin-relevant antimicrobial peptides based on enzyme alteration, substrate modification, and sequence mining. Furthermore, an updated summary of applications of nisin-relevant antimicrobial peptides has been developed for food applications. Finally, this study offers insights into emerging technologies, limitations and the future development of nisin-relevant antimicrobial peptides for pathogen inhibition, food preservatives, and improved health.

RESUMEN

Endometriosis is a multifactorial gynecological disease, with angiogenesis as a key hallmark. The role of exosomal microRNAs (miRNAs) in endometriosis is not well understood. This study investigates differentially expressed exosomal miRNAs linked to angiogenesis in endometriosis, clarifies their molecular mechanisms, and identifies potential targets. Primary endometrial stromal cells (ESCs) were cultured, and exosomes were extracted. In a co-culture system, ESC-derived exosomes were taken up by human umbilical vein endothelial cells (HUVECs). Endometriosis implant-ESC-derived exosomes (EI-EXOs) significantly promoted HUVEC proliferation, migration and tube formation compared to normal endometrium-exosomes (NE-EXOs), a finding consistent in vivo in mice. MiRNA sequencing and bioinformatics identified differentially expressed miR-21-5p from EI-EXOs, confirmed by RT-qPCR. The miR-21-5p inhibitor or GW4869 attenuated EI-EXO-induced HUVEC proliferation, migration, and tube formation. TIMP3 overexpression diminished the pro-angiogenic effect of EI-EXOs, which was reversed by adding EI-EXOs or upregulating miR-21-5p. These findings validate the crosstalk between ESCs and HUVECs mediated by exosomal miR-21-5p, and confirm the miR-21-5p-TIMP3 axis in promoting angiogenesis in endometriosis. KEY MESSAGES: ESC-derived exosomes were found to be taken up by recipient cells, i.e. HUVECs. Functionally, endometriosis implant-ESC-derived exosomes (EI-EXOs) could significantly promote the proliferation, migration and tube formation of HUVECs compared to normal endometrium-exosomes (NE-EXOs). Through miRNA sequencing and bioinformatics analysis, differentially expressed miR-21-5p released by EI-EXOs was chosen, as confirmed by qRT-PCR. miR-21-5p inhibitor or GW4869 was found to attenuate the proliferation, migration, and tube formation of HUVECs induced by EI-EXOs. In turn, TIMP3 overexpression diminished the pro-angiogenic effect of EI-EXOs, and this angiogenic phenotype was reversed once EI-EXOs were added or miR-21-5p was upregulated.

RESUMEN

This study investigated the roles of P-selectin and Clara cell secretory protein 16 (CC16) levels in the pathogenesis of severe adenovirus (ADV) pneumonia in children and evaluated their ability to predict disease. Fifty-one children (age, 1-5 years) with ADV pneumonia who were admitted to Xiamen Children's Hospital were included in this study and divided into the mild group (24 patients) and severe group (27 patients). A control group comprising healthy children of the same age who underwent routine physical examinations during the same period (30 patients) was also included. The univariate analysis demonstrated that the levels of the white blood cell count and C-reactive protein, procalcitonin, d-dimer, and P-selectin were increased in a severe group compared with a mild group, while CC16 levels were significantly decreased (p < 0.05). The logistic regression analysis revealed that P-selectin and CC16 levels were independent risk factors for severe ADV pneumonia in children. The areas under the ROC curves suggested that P-selectin and CC16 exhibited high predictive value for severe ADV pneumonia. P-selectin values more than 898.58 pg/mL and CC16 values less than 11.355 ng/mL predicted severe ADV pneumonia. P-selectin and CC16 levels are correlated with the severity of ADV pneumonia in children.

Asunto(s)

Selectina-P , Uteroglobina , Humanos , Selectina-P/sangre , Masculino , Femenino , Preescolar , Lactante , Uteroglobina/sangre , Uteroglobina/genética , Biomarcadores/sangre , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Neumonía Viral/sangre , Curva ROC , Índice de Severidad de la Enfermedad , Infecciones por Adenovirus Humanos/virología , Infecciones por Adenovirus Humanos/sangre

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Increasing evidence suggests that ferroptosis, an iron-dependent form of cell death characterized by lipid peroxidation, may play a substantial role in the traumatic brain injury (TBI) pathophysiology. 3-n-butylphthalide (NBP), a compound extracted from the seeds of Apium graveolens Linn (Chinese celery) and used in China to treat ischemic stroke, has demonstrated encouraging anti-reactive oxygen species (ROS) effects. Ascertaining whether NBP can inhibit ferroptosis and its mechanism could potentially expand its use in models of neurological injury and neurodegenerative diseases. METHODS AND RESULTS: In this study, we used erastin-induced in vitro ferroptosis models (HT22 cells, hippocampal slices, and primary neurons) and an in vivo controlled cortical impact mouse model. Our study revealed that NBP administration mitigated erastin-induced death in HT-22 cells and decreased ROS levels, lipid peroxidation, and mitochondrial superoxide indicators, resulting in mitochondrial protection. Moreover, the ability of NBP to inhibit ferroptosis was confirmed in organotypic hippocampal slice cultures and a TBI mouse model. NBP rescued neurons, inhibited microglial activation, and reduced iron levels in the brain tissue. The protective effect of NBP can be partly attributed to the inhibition of the AHR-CYP1B1 axis, as evidenced by RNA-seq and CYP1B1 overexpression/inhibition experiments in HT22 cells and primary neurons. CONCLUSIONS: Our study underscores that NBP inhibition of the AHR-CYP1B1 axis reduces ferroptosis in neuronal damage and ameliorates brain injury.

RESUMEN

Fatty liver, a major health problem worldwide, is closely associated with aberrant accumulation and alteration of energy storage organelles, lipid droplets (LDs), in the disease process. Fluorescent probes with excellent optical performance, high sensitivity/selectivity and real-time monitoring have emerged as an attractive tool for the detection of LDs used in the diagnosis of fatty liver. In this review, we summarize various probes based on different response mechanisms to image LDs in the fatty liver process using different excitation imaging modes and emission wavelengths, including the visible to the near-infrared, two/three-photon, and the second near-infrared region. The perspectives and barriers associated with the reported lipid droplet (LD) probes for future development are also discussed.

RESUMEN

Large-scale phase III clinical trials of Olaparib have revealed benefits for ovarian cancer patients with BRCA gene mutations or homologous recombination deficiency (HRD). However, fewer than 50% of ovarian cancer patients have both BRCA mutations and HRD. Therefore, improving the effect of Olaparib in HR-proficient patients is of great clinical value. Here, a combination strategy comprising Olaparib and CDK12-IN-3 effectively inhibited the growth of HR-proficient ovarian cancer in cell line, patient-derived organoid (PDO), and mouse xenograft models. Furthermore, the combination strategy induced severe DNA double-strand break (DSB) formation, increased NHEJ activity in the G2 phase, and reduced HR activity in cancer cells. Mechanistically, the combination treatment impaired Ku80 poly(ADP-ribosyl)ation (PARylation) and phosphorylation, resulting in PARP1-Ku80 complex dissociation. After dissociation, Ku80 occupancy at DSBs and the resulting Ku80-primed NHEJ activity were increased. Owing to Ku80-mediated DNA end protection, MRE11 and Rad51 foci formation was inhibited after the combination treatment, suggesting that this treatment suppressed HR activity. Intriguingly, the combination strategy expedited cGAS nuclear relocalization, further suppressing HR and, conversely, increasing genomic instability. Moreover, the inhibitory effect on cell survival persisted after drug withdrawal. These findings provide a rationale for the clinical application of CDK12-IN-3 in combination with Olaparib.

Asunto(s)

Inestabilidad Genómica , Neoplasias Ováricas , Ftalazinas , Piperazinas , Ftalazinas/farmacología , Ftalazinas/uso terapéutico , Piperazinas/farmacología , Piperazinas/uso terapéutico , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/genética , Humanos , Animales , Línea Celular Tumoral , Ratones , Inestabilidad Genómica/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Quinasas Ciclina-Dependientes/metabolismo , Autoantígeno Ku/metabolismo , Roturas del ADN de Doble Cadena/efectos de los fármacos

RESUMEN

OBJECTIVES: ZR-202-CoV and ZR-202a-CoV are novel recombinant vaccines containing 25 µg of the prototype (Wuhan strain) or B.1.351 strain (Beta variant) SARS-CoV-2 S-protein expressed in CHO cells, respectively, adjuvanted with Al(OH)3 and CpG-ODN. We assessed their safety and immunogenicity in this Phase I, randomized, observer-blind, controlled study in Mali. DESIGN: Sixty healthy 18-55-year-old adults randomized 1:1:1 received two doses of ZR-202-CoV, ZR-202a-CoV, or Comirnaty® 28 days apart. Primary outcome measures were solicited and unsolicited adverse events (AEs) including AESI (Adverse Events of Special Interest); secondary outcome was immunogenicity measured as SARS-CoV-2 specific neutralizing antibodies. Participants were followed up for 1 year. RESULTS: Injection site pain and headache were the most frequent solicited local and systemic AEs, respectively. No unsolicited AEs or SAEs related to vaccination were reported during the study period. Although most participants had detectable neutralizing antibodies at baseline robust immune responses were observed in all vaccine groups after the first dose with no further increase after the second dose. Cross-neutralizing antibody responses against Beta, Delta, and Omicron BA.5 variants were similar in magnitude after ZR-202-CoV, ZR-202a-CoV and Comirnaty®. CONCLUSIONS: Similar reactogenicity and immunogenicity profiles of ZR-202-CoV, ZR-202a-CoV and Comirnaty® support further clinical investigation in a wider population.

RESUMEN

Reactive changes of glial cells during neuroinflammation impact brain disorders and disease progression. Elucidating the mechanisms that control reactive gliosis may help us to understand brain pathophysiology and improve outcomes. Here, we report that adult ablation of autism spectrum disorder (ASD)-associated CHD8 in astrocytes attenuates reactive gliosis via remodeling chromatin accessibility, changing gene expression. Conditional Chd8 deletion in astrocytes, but not microglia, suppresses reactive gliosis by impeding astrocyte proliferation and morphological elaboration. Astrocyte Chd8 ablation alleviates lipopolysaccharide-induced neuroinflammation and septic-associated hypothermia in mice. Astrocytic CHD8 plays an important role in neuroinflammation by altering the chromatin landscape, regulating metabolic and lipid-associated pathways, and astrocyte-microglia crosstalk. Moreover, we show that reactive gliosis can be directly mitigated in vivo using an adeno-associated virus (AAV)-mediated Chd8 gene editing strategy. These findings uncover a role of ASD-associated CHD8 in the adult brain, which may warrant future exploration of targeting chromatin remodelers in reactive gliosis and neuroinflammation in injury and neurological diseases.

Asunto(s)

Astrocitos , Gliosis , Animales , Gliosis/patología , Gliosis/metabolismo , Astrocitos/metabolismo , Astrocitos/patología , Ratones , Cromatina/metabolismo , Trastorno del Espectro Autista/metabolismo , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/patología , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/patología , Ensamble y Desensamble de Cromatina , Microglía/metabolismo , Microglía/patología , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Ratones Endogámicos C57BL , Lipopolisacáridos/farmacología , Humanos , Ratones Noqueados , Masculino , Proliferación Celular

RESUMEN

Membrane-active molecular machines represent a recently emerging, yet important line of expansion in the field of artificial transmembrane transporters. Their hitherto demonstrated limited types (molecular swing, ion fishers, shuttlers, rotors, etc.) certainly call for new inspiring developments. Here, we report a very first motorized ion-transporting carrier-type transporter, i.e., a modularly tunable, light-powered propeller-like transporter derived from Feringa's molecular motor for consistently boosting transmembrane ion transport under continuous UV light irradiation. Based on the EC50 values, the molecular propeller-mediated ion transport activities under UV light irradiation for 300 s are 2.31, 1.74, 2.29, 2.80, and 2.92 times those values obtained without irradiation for Li+, Na+, K+, Rb+, and Cs+ ions, respectively, with EC50 value as low as 0.71 mol % for K+ ion under light irradiation.

RESUMEN

Enhanced dielectric constant and high breakdown strength offers immense promise for excellent energy storage performance, which is of critical significance in modern electronics and power systems. However, polymer nanocomposites with traditional routes have to balance between dielectric constant and breakdown strength, hence hindering substantive increases in energy density. Herein, a sandwiched polymer nanocomposite film has been constructed to take full advantage of the individual component layers. BaTiO3 nanoparticles are coated with a fluoropolymer to form core-shell structures and then introduced into a polymer as the top and the bottom layers of a sandwich film for enhancing polarization. Moreover, boron nitride nanosheets (BNNSs) in the middle layer of the sandwich film exert positive effects on the inhibition of current leakage for high breakdown resistance. The breakdown strength increases from 480 MV m-1 of the neat polymer to 580 MV m-1 of the sandwiched film. Additionally, the film exhibits a higher dielectric constant in comparison with the neat polymer. The sandwiched film displays a superior energy density (15.75 J cm-3), which is about 1.9 times that of the neat polymer. This work proposes a feasible route to achieve excellent energy storage of polymer dielectrics by synergistically introducing insulating fillers and additional dipoles in a sandwiched polymer nanocomposite film.

RESUMEN

AIMS: To investigate the potential linear relationship between serum concentrations of klotho and frailty. METHODS: A retrospective analysis was conducted on the data of 9,597 middle-aged and older adults (aged 40-79 years) from the five cycles of the National Health and Nutrition Examination Survey (NHANES). Frailty was assessed using the Frailty Index, calculated as a percentage of accumulated deficits across 53 health items. Restricted cubic spline curves, subgroup analyses and logistic regression models were employed to evaluate the specific linear trend connection between circulating klotho protein concentration and frailty. RESULTS: When taking Klotho into account as a continuous component in Models 1 and 2, there was a substantial association between the increasing Klotho level and the reduced risk of frailty. Model 3 revealed a strong negative correlation between the Klotho and Frailty, suggesting that high levels of Klotho protein decreases the frailty prevalence [Odd ratio (OR): 0.25; 95% confidence interval (CI): 0.15-0.43]. Furthermore, according to the quartile analyses, after fully adjusting for the covariates, it was observed that, comparing to the lowest quartile of Klotho, the highest quartile of Klotho demonstrated lowest risk of frailty (OR 0.69; 95% CI 0.58-0.81, Ptrend < 0.001). The restricted cubic spline curves showed a linear relationship and an inverse association between frailty and the Klotho levels (Plinearity < 0.001; Pnon-linearity = 0.736). CONCLUSION: Klotho is inversely and linearly associated with physical frailty in the general population (aged 40-79 years), specifically in the population with an age < 65 and body mass index (BMI) ≥ 25 kg/m2. More necessary prospective studies should be done to further investigate the mechanisms underlying frailty and aging and to elucidate individual frailty causes.

RESUMEN

Circular RNAs (circRNAs) play vital roles in transcription and translation. Identification of circRNA-RBP (RNA-binding protein) interaction sites has become a fundamental step in molecular and cell biology. Deep learning (DL)-based methods have been proposed to predict circRNA-RBP interaction sites and achieved impressive identification performance. However, those methods cannot effectively capture long-distance dependencies, and cannot effectively utilize the interaction information of multiple features. To overcome those limitations, we propose a DL-based model iCRBP-LKHA using deep hybrid networks for identifying circRNA-RBP interaction sites. iCRBP-LKHA adopts five encoding schemes. Meanwhile, the neural network architecture, which consists of large kernel convolutional neural network (LKCNN), convolutional block attention module with one-dimensional convolution (CBAM-1D) and bidirectional gating recurrent unit (BiGRU), can explore local information, global context information and multiple features interaction information automatically. To verify the effectiveness of iCRBP-LKHA, we compared its performance with shallow learning algorithms on 37 circRNAs datasets and 37 circRNAs stringent datasets. And we compared its performance with state-of-the-art DL-based methods on 37 circRNAs datasets, 37 circRNAs stringent datasets and 31 linear RNAs datasets. The experimental results not only show that iCRBP-LKHA outperforms other competing methods, but also demonstrate the potential of this model in identifying other RNA-RBP interaction sites.

Asunto(s)

Algoritmos , Biología Computacional , Aprendizaje Profundo , Redes Neurales de la Computación , ARN Circular , Proteínas de Unión al ARN , ARN Circular/genética , ARN Circular/metabolismo , Biología Computacional/métodos , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Humanos , Sitios de Unión/genética

RESUMEN

Small-molecule fluorescent probes have emerged as potential tools for cancer cell imaging-based diagnostic and therapeutic applications, but their limited selectivity and poor imaging contrast hinder their broad applications. To address these problems, we present the design and construction of a novel near-infrared (NIR) biotin-conjugated and viscosity-activatable fluorescent probe, named as QL-VB, for selective recognition and imaging of cancer cells. The designed probe exhibited a NIR emission at 680 nm, with a substantial Stokes shift of 100 nm and remarkably sensitive responses toward viscosity changes in solution. Importantly, QL-VB provided an evidently enhanced signal-to-noise ratio (SNR: 6.2) for the discrimination of cancer cells/normal cells, as compared with the control probe without biotin conjugation (SNR: 1.8). Moreover, we validated the capability of QL-VB for dynamic monitoring of stimulated viscosity changes within cancer cells and employed QL-VB for distinguishing breast cancer tissues from normal tissues in live mice with improved accuracy (SNR: 2.5) in comparison with the control probe (SNR: 1.8). All these findings indicated that the cancer-targeting and viscosity-activatable NIR fluorescent probe not only enables the mechanistic investigations of mitochondrial viscosity alterations within cancer cells but also holds the potential as a robust tool for cancer cell imaging-based applications.

Asunto(s)

Colorantes Fluorescentes , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Viscosidad , Animales , Ratones , Imagen Óptica , Femenino , Rayos Infrarrojos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Línea Celular Tumoral , Biotina/química

RESUMEN

INTRODUCTION: 4q35 deletion is a rare chromosomal syndrome with a wide range of phenotypes, which can be challenging to detect through prenatal ultrasound. This study aimed to summarize the fetal phenotypes of patients with 4q35 deletion. CASE PRESENTATION: The study included four fetuses with 4q35 deletion, with detailed records of prenatal ultrasound and genetic testing results. These cases included following phenotypes, fetal growth restriction (FGR) (2/4), cystic hygroma (2/4), single umbilical artery (1/4), and fused kidney (1/4). One case was terminated, while the other three were born and showed no obvious abnormalities at the 1-year follow-up. Previous reports have described the fetal phenotype of 4q35 deletion in 6 patients from five families, with prenatal phenotypes including FGR (2/6), cardiac structural abnormalities (1/6), brain ventriculomegaly (1/6), oligohydramnios (1/6), and multicystic dysplastic kidneys (1/6). CONCLUSION: Overall, the phenotypes of fetuses with 4q35 deletion are diverse, with FGR potentially being a significant phenotype in these cases.

RESUMEN

Microplastics (MPs) as emerging contaminants are widely present in the environment and are ubiquitously ingested and accumulated by aquatic organisms. MPs may be quickly eliminated after a brief retention in aquatic animals (such as the digestive tract); thus, understanding the damage caused by MPs during this process and whether the damage can be recovered is important. Here, we proposed the use of visible light imaging to track MPs combined with near-infrared (NIR) imaging to reveal the in situ impacts of MPs. The combination of these two techniques allows for the simultaneous investigation of the localization and functionality of MPs in vivo. We investigated the effects of two types of MPs on zebrafish, microplastic fibers (MFs) and microplastic beads (MBs). The results showed that MPs larger than 10 µm primarily accumulated in the intestines of zebrafish. Both MFs and MBs disrupted the redox balance of the intestine, and the location of the damage was consistent with the heterogeneous accumulation of MPs. MFs caused greater and more difficult-to-recover damage compared to MBs, which was closely related to the slower elimination rate of MFs. Our study highlights the importance of capturing the dynamic toxicological effects of MPs on organisms. Fibrous MPs and spherical MPs clearly had distinct effects on their toxicokinetics and toxicodynamics in fish.

Asunto(s)

Microplásticos , Pez Cebra , Animales , Microplásticos/toxicidad , Contaminantes Químicos del Agua/toxicidad

RESUMEN

INTRODUCTION: Breast cancer has become the most common cancer worldwide. Various types of mindfulness-based interventions (e.g., mindfulness-based cognitive therapy, mindfulness-based stress reduction) have been conducted in different delivery methods (including face to face and internet delivered) to help patients with breast cancer mitigate their depression. However, at present, there are no studies that compare the effectiveness of all these types and deliveries of mindfulness-based interventions. Therefore, this protocol aims to conduct a systematic review and network meta-analysis to assess the effectiveness of various types and deliveries of mindfulness-based interventions in mitigating depression in patients with breast cancer. METHODS: This protocol is according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The electronic databases, including PubMed, Web of Science, the Cochrane Library, Embase, Google Scholar, The China National Knowledge Infrastructure and OpenGrey, will be comprehensively retrieved for related randomised controlled trials (RCTs) from inception to December 2023. Two reviewers will independently assess the risk of bias using the Cochrane Risk of Bias Tool for Randomised Trials 2.0 (RoB 2.0). The network meta-analysis will be performed using the STATA V.16.0, and the assessment of heterogeneity, inconsistency, publication bias, evidence quality, subgroup analyses and sensitivity analyses will be conducted. ETHICS AND DISSEMINATION: This protocol does not require approval from an ethics committee as it is based on previous research findings. The results will be disseminated via peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42024495996.

Asunto(s)

Neoplasias de la Mama , Depresión , Atención Plena , Metaanálisis en Red , Revisiones Sistemáticas como Asunto , Femenino , Humanos , Neoplasias de la Mama/terapia , Neoplasias de la Mama/psicología , Depresión/terapia , Depresión/etiología , Atención Plena/métodos , Proyectos de Investigación

RESUMEN

Antimicrobial resistance has been an increasingly serious threat to global public health. The contribution of non-antibiotic pharmaceuticals to the development of antibiotic resistance has been overlooked. Our study found that the anti-inflammatory drug phenylbutazone could protect P. aeruginosa against antibiotic mediated killing by binding to the efflux pump regulator MexR. In this study, antibiotic activity against P. aeruginosa alone or in combination with phenylbutazone was evaluated in vitro and in vivo. Resazurin accumulation assay, transcriptomic sequencing, and PISA assay were conducted to explore the underlying mechanism for the reduced antibiotic susceptibility caused by phenylbutazone. Then EMSA, ITC, molecular dynamic simulations, and amino acid substitutions were used to investigate the interactions between phenylbutazone and MexR. We found that phenylbutazone could reduce the susceptibility of P. aeruginosa to multiple antibiotics, including parts of ß-lactams, fluoroquinolones, tetracyclines, and macrolides. Phenylbutazone could directly bind to MexR, then promote MexR dissociating from the mexA-mexR intergenic region and de-repress the expression of MexAB-OprM efflux pump. The overexpressed MexAB-OprM pump resulted in the reduced antibiotic susceptibility. And the His41 and Arg21 residues of MexR were involved in the phenylbutazone-MexR interaction. We hope this study would imply the potential risk of antibiotic resistance caused by non-antibiotic pharmaceuticals.

Asunto(s)

Antibacterianos , Proteínas Bacterianas , Proteínas de Transporte de Membrana , Pruebas de Sensibilidad Microbiana , Fenilbutazona , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Antibacterianos/farmacología , Antibacterianos/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Proteínas de Transporte de Membrana/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Fenilbutazona/farmacología , Fenilbutazona/metabolismo , Proteínas de la Membrana Bacteriana Externa/metabolismo , Proteínas de la Membrana Bacteriana Externa/genética , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Simulación de Dinámica Molecular , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/tratamiento farmacológico , Fluoroquinolonas/farmacología , Fluoroquinolonas/metabolismo , Unión Proteica , Animales

RESUMEN

Objective: To explore the treatment effect and potential mechanism on gut microbiota, nutrition, and metabolism of Fufang Duzheng Tablet (DZGP) on rheumatoid arthritis (RA). Methods: Collagen-induced arthritis rats' models were established and divided into three groups: model control group (FK), DZGP group (FZ, 0.45 g/kg/d), and methotrexate group (FM, 1.35 mg/kg), which were treated by gavage for 28 days. The physiopathologic changes of joints and body weight in each group were recorded; the morphology of synovial and ankle tissues was observed by hematoxylin-eosin staining, and the level of serum TNF-α and IL-1ß was tested by ELISA. UPLC/MS-MS and network pharmacological analysis were used to identify the serum components, and 16S rDNA sequencing analysis was applied to the intestinal contents of rats. Results: DZGP treatment significantly alleviated arthritis symptoms, pathological manifestations, toe thickness, and TNF-α and IL-1ß levels in RA rats. We identified 105 metabolites and 18 components in the serum of DZGP-group rats. The main therapeutic targets of DZGP for anti-RA were TP53, epidermal growth factor receptor, and AKT1. Molecular docking showed that there was good binding efficiency between core components and main targets. 16S rDNA sequencing showed that DZGP treatment regulated the structure of the gut microbiota. Conclusion: DZGP showed a good anti-inflammatory effect on RA and played an important role in improving the structure of the gut microbiota in RA rats.

RESUMEN

Systemic inflammatory response index (SIRI) has been proven to be associated with the prognosis of coronary artery disease and many other diseases. However, the relationship between SIRI and acute traumatic spinal cord injury (tSCI) has rarely been evaluated. The study aims to assess the prognostic value of SIRI for clinical outcomes in individuals with acute tSCI. A total of 190 patients admitted within eight hours after tSCI between January 2021 and April 2023 were enrolled in our study. Logistic regression analysis was used to analyze the association between SIRI and American Spinal Injury Association Impairment Scale (AIS) grade at admission and discharge, as well as neurological improvement in tSCI patients, and receiver operating characteristic (ROC) analysis was performed to assess the discriminative ability of SIRI in predicting AIS grade at discharge. After adjusting for confounding factors, SIRI positively correlated with the AIS grade (A to C) at admission and discharge, and negatively correlated with neurological improvement. The area under the curve values in ROC analysis was 0.725 (95% CI 0.647, 0.803). The study suggests that SIRI is significantly associated with an increased risk of poor clinical outcome at discharge in tSCI patients and has a certain discriminative value.

Asunto(s)

Curva ROC , Traumatismos de la Médula Espinal , Humanos , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Adulto , Anciano , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Estudios Retrospectivos