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1.
Crit Rev Anal Chem ; : 1-20, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38978228

RESUMEN

Bladder cancer (BC) is the tenth most common cancer globally, predominantly affecting men. Early detection and treatment are crucial due to high recurrence rates and poor prognosis for advanced stages. Traditional diagnostic methods like cystoscopy and imaging have limitations, leading to the exploration of noninvasive methods such as liquid biopsy. This review highlights the application of biosensors in BC, including electrochemical and optical sensors for detecting tumor markers like proteins, nucleic acids, and other biomolecules, noting their clinical relevance. Emerging therapeutic approaches, such as antibody-drug conjugates, targeted therapy, immunotherapy, and gene therapy, are also explored, the role of biosensors in detecting corresponding biomarkers to guide these treatments is examined. Finally, the review addresses the current challenges and future directions for biosensor applications in BC, highlighting the need for large-scale clinical trials and the integration of advanced technologies like deep learning to enhance diagnostic accuracy and treatment efficacy.

2.
Sci Rep ; 14(1): 16942, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043787

RESUMEN

Quantum computing, with its superior computational capabilities compared to classical approaches, holds the potential to revolutionize numerous scientific domains, including pharmaceuticals. However, the application of quantum computing for drug discovery has primarily been limited to proof-of-concept studies, which often fail to capture the intricacies of real-world drug development challenges. In this study, we diverge from conventional investigations by developing a hybrid quantum computing pipeline tailored to address genuine drug design problems. Our approach underscores the application of quantum computation in drug discovery and propels it towards more scalable system. We specifically construct our versatile quantum computing pipeline to address two critical tasks in drug discovery: the precise determination of Gibbs free energy profiles for prodrug activation involving covalent bond cleavage, and the accurate simulation of covalent bond interactions. This work serves as a pioneering effort in benchmarking quantum computing against veritable scenarios encountered in drug design, especially the covalent bonding issue present in both of the case studies, thereby transitioning from theoretical models to tangible applications. Our results demonstrate the potential of a quantum computing pipeline for integration into real world drug design workflows.


Asunto(s)
Descubrimiento de Drogas , Teoría Cuántica , Descubrimiento de Drogas/métodos , Diseño de Fármacos/métodos , Profármacos/química , Termodinámica
3.
Talanta ; 277: 126395, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38865958

RESUMEN

In this study, an original molecularly imprinted electrochemical sensor (MIECS) is prepared using layer-by-layer modification of sensitization nanomaterials (CuCo2O4/BPC-E) coupled with molecularly imprinted polymers (MIPs) for the ultrasensitive and rapid determination of dimetridazole (DMZ) contaminants. The biomass waste of eggshell (ES) powders subtly introduced in situ in the carbonization process of psyllium husk (PSH) substantially promotes the physicochemical properties of the resulting biomass-derived porous carbon (BPC-E). The large specific surface area and abundant pores provide a favourable surface for loading mesoporous CuCo2O4 with a spinel structure. The assembly of CuCo2O4/BPC-E on the gold electrode (GE) surface enhances the electrochemical sensing signal. The MIPs constructed using DMZ and o-phenylenediamine (oPD) as templates and functional monomers boost the targeted recognition performance of the analyte. The combined DMZ targets then undergo an electrochemical reduction reaction in situ with the transfer of four electrons and four protons. Under optimum conditions, the current response of differential pulse voltammetry (DPV) exhibits two linear ranges for DMZ detection, 0.01-10 µM and 10-200 µM. The limit of detection (LOD) is 1.8 nM (S/N = 3) with a sensitivity of 5.724 µA µM-1 cm-2. The obtained MIECS exhibits excellent selectivity, reproducibility, repeatability and stability. This electrochemical sensing system is applied to the detection of real samples (tap water, coarse fodder and swine urine), yielding satisfactory recoveries (90.6%-98.1 %), which are consistent with those obtained via HPLC. This finding verifies that the utility of MIECS for monitoring pharmaceutical and environmental contaminants and ensuring food safety.


Asunto(s)
Carbono , Técnicas Electroquímicas , Polímeros Impresos Molecularmente , Nanocompuestos , Nanocompuestos/química , Porosidad , Carbono/química , Polímeros Impresos Molecularmente/química , Técnicas Electroquímicas/métodos , Biomasa , Límite de Detección , Animales , Cobre/química , Electrodos , Contaminantes Químicos del Agua/análisis
4.
Expert Opin Ther Pat ; 34(8): 701-721, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38884569

RESUMEN

INTRODUCTION: KRAS is a critical oncogenic protein intricately involved in tumor progression, and the difficulty in targeting KRAS has led it to be classified as an 'undruggable target.' Among the various KRAS mutations, KRASG12D is highly prevalent and represents a promising therapeutic target, yet there are currently no approved inhibitors for it. AREA COVERED: This review summarizes numerous patents and literature featuring inhibitors or degraders of KRASG12D through searching relevant information in PubMed, SciFinder and Web of Science databases from 2021 to February 2024, providing an overview of the research progress on inhibiting KRASG12D in terms of design strategies, chemical structures, biological activities, and clinical advancements. EXPERT OPINION: Since the approval of AMG510 (Sotorasib), there has been an increasing focus on the inhibition of KRASG12D, leading to numerous reports of related inhibitors and degraders. Among them, MRTX1133, as the first KRASG12D inhibitor to enter clinical trials, has demonstrated excellent tumor suppression in various KRASG12D-bearing human tumor xenograft models. It is important to note, however, that understanding the mechanisms of acquired resistance caused by KRAS inhibition and developing additional combination therapies is crucial. Moreover, seeking covalent inhibition of KRASG12D also holds significant potential.


Asunto(s)
Antineoplásicos , Neoplasias , Patentes como Asunto , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Animales , Antineoplásicos/farmacología , Proteínas Proto-Oncogénicas p21(ras)/antagonistas & inhibidores , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Mutación , Diseño de Fármacos , Desarrollo de Medicamentos , Resistencia a Antineoplásicos , Terapia Molecular Dirigida , Piperazinas , Piridinas , Pirimidinas
5.
Clin Case Rep ; 12(6): e9024, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38883220

RESUMEN

Key Clinical Message: Good's syndrome (GS) presents with thymoma, hypogammaglobulinemia, and recurrent infection. The manifestations of patients diagnosed with GS and Cytomegalovirus (CMV) gastroenteritis are rare and non-specific. Early diagnosis and treatment can improve the prognosis of the rare disease. Abstract: Good's syndrome (GS), a rare acquired immunodeficiency condition, is characterized by thymoma, hypogammaglobulinemia, and low peripheral B-lymphocyte count. GS tends to occur in individuals aged 40-60 years, resulting in increased risk of recurrent infections with various conditional pathogenic bacteria, viruses, and fungi. Cytomegalovirus (CMV) can cause pneumonia, retinitis, encephalitis, and enteritis in GS patient, but CMV infection in the alimentary tract is usually underestimated, delayed diagnosed and misdiagnosed. In this study, we reported a female patient with GS and chronic diarrhea due to CMV infection and reviewed the literature to conclude the characteristics of this rare condition to improve the clinical diagnosis and prognosis of CMV gastroenteritis in patients with GS.

6.
Oncol Lett ; 28(2): 339, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38855503

RESUMEN

3,3'-Diindolylmethane (DIM) is a natural phytochemical derived from cruciferous plants that has inhibitory effects on a wide range of tumor cells; however, its relevant effects on esophageal cancer cells have been poorly studied. Therefore, in the present study, a pharmacology network approach was used to predict the possible core targets of DIM acting on esophageal cancer. Subsequently, using in vitro experiments, TE-1 human esophageal cancer cells were treated with different concentrations of DIM (0, 40, 60 and 80 µM) for 24 h. Changes in cell activity were detected by Cell Counting Kit-8 assay, and changes in the expression levels of stromal interaction molecule 1 (STIM1) and apoptosis-related proteins, B-cell lymphoma-2 (Bcl-2) and Bax, were assessed by western blotting, followed by the upregulation of STIM1 by thapsigargin (Tg). Network pharmacology analysis showed that there were 39 potential core targets of DIM in esophageal cancer. The results of the in vitro experiments showed that DIM could inhibit the viability of esophageal cancer cells, downregulate the expression of STIM1 and Bcl-2 proteins and upregulate the expression of Bax protein, all in a concentration-dependent manner. The results also demonstrated that toxic carotenoids were agonist against STIM1 protein and upregulated STIM1 and Bax protein expression. After agonizing STIM1 protein expression using Tg, DIM was able to counteract the expression trend of STIM1, Bcl-2 and Bax protein in TE-1 cells. In summary, DIM induced apoptosis and inhibited the viability of esophageal cancer cells by downregulating the expression of STIM1 protein; therefore, the natural phytochemical, DIM, may be a potential substance for the early prevention and treatment of esophageal cancer cells.

7.
Shock ; 62(1): 74-84, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38713551

RESUMEN

ABSTRACT: Ischemia-reperfusion injury (IRI) often stems from an imbalance between mitochondrial dynamics and autophagy. Melatonin mitigates IRI by regulating mitochondrial dynamics. However, the precise molecular mechanism underlying the role of melatonin in reducing IRI through modulating mitochondrial dynamics remains elusive. The objective of this study was to investigate whether pretreatment with melatonin before IRI confers protective effects by modulating mitochondrial dynamics and mitophagy. Melatonin pretreatment was administered to HK-2 cells and live rats before subjecting them to hypoxia-reoxygenation or IRI, respectively. Cells and rat kidney models were evaluated for markers of oxidative stress, autophagy, mitochondrial dynamics, and the expression of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and phospho-AMPKα (P-AMPK). After renal IRI, increased mitochondrial fission and autophagy were observed, accompanied by exacerbated cellular oxidative stress injury and aggravated mitochondrial dysfunction. Nevertheless, melatonin pretreatment inhibited mitochondrial fission, promoted mitochondrial fusion, and attenuated autophagy levels. This intervention was correlated with a notable reduction in oxidative stress injury and remarkable restoration of mitochondrial functionality. Ischemia-reperfusion injury led to a decline in P-AMPK levels, whereas melatonin pretreatment increased the level of P-AMPK levels. Silencing AMPK with small interfering RNA exacerbated mitochondrial damage, and in this context, melatonin pretreatment did not alleviate mitochondrial fission or autophagy levels but resulted in sustained oxidative stress damage. Collectively, these findings indicate that melatonin pretreatment shields the kidneys from IRI by mitigating excessive mitochondrial fission, moderating autophagy levels, and preserving appropriate mitochondrial fission, all in an AMPK-dependent manner.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Autofagia , Melatonina , Dinámicas Mitocondriales , Daño por Reperfusión , Melatonina/farmacología , Melatonina/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Animales , Dinámicas Mitocondriales/efectos de los fármacos , Autofagia/efectos de los fármacos , Ratas , Proteínas Quinasas Activadas por AMP/metabolismo , Masculino , Dinaminas/metabolismo , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Riñón/irrigación sanguínea , Estrés Oxidativo/efectos de los fármacos , Humanos , Ratas Sprague-Dawley , Línea Celular , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo
8.
ACS Nano ; 18(19): 12341-12354, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38695772

RESUMEN

The patch with a superlubricated surface shows great potential for the prevention of postoperative adhesion during soft tissue repair. However, the existing patches suffer from the destruction of topography during superlubrication coating and lack of pro-healing capability. Herein, we demonstrate a facile and versatile strategy to develop a Janus nanofibrous patch (J-NFP) with antiadhesion and reactive oxygen species (ROS) scavenging functions. Specifically, sequential electrospinning is performed with initiators and CeO2 nanoparticles (CeNPs) embedded on the different sides, followed by subsurface-initiated atom transfer radical polymerization for grafting zwitterionic polymer brushes, introducing superlubricated skin on the surface of single nanofibers. The poly(sulfobetaine methacrylate) brush-grafted patch retains fibrous topography and shows a coefficient of friction of around 0.12, which is reduced by 77% compared with the pristine fibrous patch. Additionally, a significant reduction in protein, platelet, bacteria, and cell adhesion is observed. More importantly, the CeNPs-embedded patch enables ROS scavenging as well as inhibits pro-inflammatory cytokine secretion and promotes anti-inflammatory cytokine levels. Furthermore, the J-NFP can inhibit tissue adhesion and promote repair of both rat skin wounds and intrauterine injuries. The present strategy for developing the Janus patch exhibits enormous prospects for facilitating soft tissue repair.


Asunto(s)
Nanofibras , Animales , Ratas , Nanofibras/química , Cicatrización de Heridas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Piel/efectos de los fármacos , Piel/patología , Adherencias Tisulares/prevención & control , Ratas Sprague-Dawley , Adhesión Celular/efectos de los fármacos , Cerio/química , Cerio/farmacología , Propiedades de Superficie , Ratones , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología
9.
Diagnostics (Basel) ; 14(10)2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38786304

RESUMEN

BACKGROUND: The aim of this study was to exploit integrated PET/MRI to simultaneously evaluate the morphological, component, and metabolic features of advanced atherosclerotic plaques and explore their incremental value. METHODS: In this observational prospective cohort study, patients with advanced plaque in the carotid artery underwent 18F-FDG PET/MRI. Plaque morphological features were measured, and plaque component features were determined via MRI according to AHA lesion-types. Maximum standardized uptake values (SUVmax) and tissue to background ratio (TBR) on PET were calculated. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of FDG uptake when added to AHA lesion-types for symptomatic plaque classification. RESULTS: A total of 280 patients with advanced plaque in the carotid artery were recruited. A total of 402 plaques were confirmed, and 87 of 402 (21.6%) were symptomatic plaques. 18F-FDG PET/MRI was performed a mean of 38 days (range 1-90) after the symptom. Increased stenosis degree (61.5% vs. 50.0%, p < 0.001) and TBR (2.96 vs. 2.32, p < 0.001) were observed in symptomatic plaques compared with asymptomatic plaques. The performance of the combined model (AHA lesion type VI + stenosis degree + TBR) for predicting symptomatic plaques was the best among all models (AUC = 0.789). The improvement of the combined model (AHA lesion type VII + stenosis degree + TBR) over AHA lesion type VII model for predicting symptomatic plaques was the highest (AUC = 0.757/0.454, combined model/AHA lesion type VII model), and the NRI was 50.7%. CONCLUSIONS: Integrated PET/MRI could simultaneously evaluate the morphological component and inflammation features of advanced atherosclerotic plaques and provide supplementary optimization information over AHA lesion-types for identifying vulnerable plaques in atherosclerosis subjects to achieve further stratification of stroke risk.

10.
Neuroimage ; 294: 120640, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38719154

RESUMEN

Attentional control, guided by top-down processes, enables selective focus on pertinent information, while habituation, influenced by bottom-up factors and prior experiences, shapes cognitive responses by emphasizing stimulus relevance. These two fundamental processes collaborate to regulate cognitive behavior, with the prefrontal cortex and its subregions playing a pivotal role. Nevertheless, the intricate neural mechanisms underlying the interaction between attentional control and habituation are still a subject of ongoing exploration. To our knowledge, there is a dearth of comprehensive studies on the functional connectivity between subsystems within the prefrontal cortex during attentional control processes in both primates and humans. Utilizing stereo-electroencephalogram (SEEG) recordings during the Stroop task, we observed top-down dominance effects and corresponding connectivity patterns among the orbitofrontal cortex (OFC), the middle frontal gyrus (MFG), and the inferior frontal gyrus (IFG) during heightened attentional control. These findings highlighting the involvement of OFC in habituation through top-down attention. Our study unveils unique connectivity profiles, shedding light on the neural interplay between top-down and bottom-up attentional control processes, shaping goal-directed attention.


Asunto(s)
Atención , Electroencefalografía , Habituación Psicofisiológica , Corteza Prefrontal , Humanos , Corteza Prefrontal/fisiología , Corteza Prefrontal/diagnóstico por imagen , Atención/fisiología , Masculino , Femenino , Electroencefalografía/métodos , Habituación Psicofisiológica/fisiología , Adulto , Adulto Joven , Test de Stroop
11.
Adv Sci (Weinh) ; 11(26): e2402816, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38666376

RESUMEN

Leaf shape is considered to be one of the most significant agronomic traits in crop breeding. However, the molecular basis underlying leaf morphogenesis in cotton is still largely unknown. In this study, through genetic mapping and molecular investigation using a natural cotton mutant cu with leaves curling upward, the causal gene GHCU is successfully identified as the key regulator of leaf flattening. Knockout of GHCU or its homolog in cotton and tobacco using CRISPR results in abnormal leaf shape. It is further discovered that GHCU facilitates the transport of the HD protein KNOTTED1-like (KNGH1) from the adaxial to the abaxial domain. Loss of GHCU function restricts KNGH1 to the adaxial epidermal region, leading to lower auxin response levels in the adaxial boundary compared to the abaxial. This spatial asymmetry in auxin distribution produces the upward-curled leaf phenotype of the cu mutant. By analysis of single-cell RNA sequencing and spatiotemporal transcriptomic data, auxin biosynthesis genes are confirmed to be expressed asymmetrically in the adaxial-abaxial epidermal cells. Overall, these findings suggest that GHCU plays a crucial role in the regulation of leaf flattening through facilitating cell-to-cell trafficking of KNGH1 and hence influencing the auxin response level.


Asunto(s)
Gossypium , Hojas de la Planta , Proteínas de Plantas , Gossypium/genética , Gossypium/metabolismo , Hojas de la Planta/metabolismo , Hojas de la Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Fenotipo , Regulación de la Expresión Génica de las Plantas/genética , Ácidos Indolacéticos/metabolismo
12.
Int J Biol Macromol ; 269(Pt 1): 131813, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38685537

RESUMEN

Microbial exopolysaccharides (EPS) have various physiological functions such as antioxidant, anti-tumor, cholesterol lowering, and immune regulation. However, improving traditional fermentation conditions to increase the production of EPS from Lactiplantibacillus plantarum (L. plantarum) is limited. In this study, we aimed to better improve EPS production and physiological functions of L. plantarum YM-4-3 strain by overexpressing and knocking out the priming glycosyltransferase genes cps 2E and cps 4E for the first time. As a result, the EPS production of the overexpression strain was 30.15 %, 26.84 % and 36.29 % higher than WT, respectively. The EPS production of the knockout strain was significantly lower than that of the WT. At the same time, transcriptome data showed that the gene expression levels of each experimental strain had changed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways found that the glycolysis/gluconeogenesis pathway had the highest gene enrichment in the metabolic pathway. The monosaccharide components of the EPS of each experimental strain were different from those of the WT and the EPS of the experimental strain showed stronger activity against oxidation. In conclusion, this study contributes to the efficient production and application of L. plantarum EPS and helps to understand the mechanism of EPS regulation in L. plantarum.


Asunto(s)
Glicosiltransferasas , Lactobacillus plantarum , Polisacáridos Bacterianos , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismo , Polisacáridos Bacterianos/biosíntesis , Lactobacillus plantarum/genética , Lactobacillus plantarum/metabolismo , Regulación Bacteriana de la Expresión Génica , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Fermentación
13.
Exp Hematol Oncol ; 13(1): 37, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38570883

RESUMEN

Adoptive immunotherapy in the T cell landscape exhibits efficacy in cancer treatment. Over the past few decades, genetically modified T cells, particularly chimeric antigen receptor T cells, have enabled remarkable strides in the treatment of hematological malignancies. Besides, extensive exploration of multiple antigens for the treatment of solid tumors has led to clinical interest in the potential of T cells expressing the engineered T cell receptor (TCR). TCR-T cells possess the capacity to recognize intracellular antigen families and maintain the intrinsic properties of TCRs in terms of affinity to target epitopes and signal transduction. Recent research has provided critical insight into their capability and therapeutic targets for multiple refractory solid tumors, but also exposes some challenges for durable efficacy. In this review, we describe the screening and identification of available tumor antigens, and the acquisition and optimization of TCRs for TCR-T cell therapy. Furthermore, we summarize the complete flow from  laboratory to clinical applications of TCR-T cells. Last, we emerge future prospects for improving therapeutic efficacy in cancer world with combination therapies or TCR-T derived products. In conclusion, this review depicts our current understanding of TCR-T cell therapy in solid neoplasms, and provides new perspectives for expanding its clinical applications and improving therapeutic efficacy.

14.
Front Big Data ; 7: 1346958, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650693

RESUMEN

Introduction: Acupuncture and tuina, acknowledged as ancient and highly efficacious therapeutic modalities within the domain of Traditional Chinese Medicine (TCM), have provided pragmatic treatment pathways for numerous patients. To address the problems of ambiguity in the concept of Traditional Chinese Medicine (TCM) acupuncture and tuina treatment protocols, the lack of accurate quantitative assessment of treatment protocols, and the diversity of TCM systems, we have established a map-filling technique for modern literature to achieve personalized medical recommendations. Methods: (1) Extensive acupuncture and tuina data were collected, analyzed, and processed to establish a concise TCM domain knowledge base. (2)A template-free Chinese text NER joint training method (TemplateFC) was proposed, which enhances the EntLM model with BiLSTM and CRF layers. Appropriate rules were set for ERE. (3) A comprehensive knowledge graph comprising 10,346 entities and 40,919 relationships was constructed based on modern literature. Results: A robust TCM KG with a wide range of entities and relationships was created. The template-free joint training approach significantly improved NER accuracy, especially in Chinese text, addressing issues related to entity identification and tokenization differences. The KG provided valuable insights into acupuncture and tuina, facilitating efficient information retrieval and personalized treatment recommendations. Discussion: The integration of KGs in TCM research is essential for advancing diagnostics and interventions. Challenges in NER and ERE were effectively tackled using hybrid approaches and innovative techniques. The comprehensive TCM KG our built contributes to bridging the gap in TCM knowledge and serves as a valuable resource for specialists and non-specialists alike.

15.
Physiol Meas ; 45(5)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38599216

RESUMEN

Objective. Diagnosing chronic obstructive pulmonary disease (COPD) using impulse oscillometry (IOS) is challenging due to the high level of clinical expertise it demands from doctors, which limits the clinical application of IOS in screening. The primary aim of this study is to develop a COPD diagnostic model based on machine learning algorithms using IOS test results.Approach. Feature selection was conducted to identify the optimal subset of features from the original feature set, which significantly enhanced the classifier's performance. Additionally, secondary features area of reactance (AX) were derived from the original features based on clinical theory, further enhancing the performance of the classifier. The performance of the model was analyzed and validated using various classifiers and hyperparameter settings to identify the optimal classifier. We collected 528 clinical data examples from the China-Japan Friendship Hospital for training and validating the model.Main results. The proposed model achieved reasonably accurate diagnostic results in the clinical data (accuracy = 0.920, specificity = 0.941, precision = 0.875, recall = 0.875).Significance. The results of this study demonstrate that the proposed classifier model, feature selection method, and derived secondary feature AX provide significant auxiliary support in reducing the requirement for clinical experience in COPD diagnosis using IOS.


Asunto(s)
Aprendizaje Automático , Oscilometría , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Humanos , Oscilometría/métodos , Masculino , Femenino , Persona de Mediana Edad , Algoritmos , Anciano
16.
Cancer Metab ; 12(1): 7, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38395945

RESUMEN

BACKGROUND: Hypoxia contributes to cancer progression through various molecular mechanisms and hepatocellular carcinoma (HCC) is one of the most hypoxic malignancies. Hypoxia-inducible gene domain protein-1a (HIGD1A) is typically induced via epigenetic regulation and promotes tumor cell survival during hypoxia. However, the role of HIGD1A in HCC remains unknown. METHODS: HIGD1A expression was determined in 24 pairs of human HCC samples and para-tumorous tissues. Loss-of-function experiments were conducted both in vivo and in vitro to explore the role of HIGD1A in HCC proliferation and metastasis. RESULTS: Increased HIGD1A expression was found in HCC tissues and cell lines, which was induced by hypoxia or low-glucose condition. Moreover, HIGD1A knockdown in HCC cells arrested the cell cycle at the G2/M phase and promoted hypoxia-induced cell apoptosis, resulting in great inhibition of cell proliferation, migration, and invasion, as well as tumor xenograft formation. Interestingly, these anti-tumor effects were not observed in normal hepatocyte cell line L02. Further, HIGD1A knockdown suppressed the expression of ornithine decarboxylase 1 (ODC1), a rate-limiting enzyme of polyamine metabolism under c-Myc regulation. HIGD1A was found to bind with the c-Myc promoter region, and its knockdown decreased the levels of polyamine metabolites. Consistently, the inhibitory effect on HCC phenotype by HIGD1A silencing could be reversed by overexpression of c-Myc or supplementation of polyamines. CONCLUSIONS: Our results demonstrated that HIGD1A activated c-Myc-ODC1 nexus to regulate polyamine synthesis and to promote HCC survival and malignant phenotype, implying that HIGD1A might represent a novel therapeutic target for HCC.

17.
J Transl Med ; 22(1): 125, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38303030

RESUMEN

BACKGROUND: Previous studies have shown that changes in the microbial community of the female urogenital tract are associated with Human papillomavirus (HPV) infection. However, research on this association was mostly focused on a single site, and there are currently few joint studies on HPV infection and multiple sites in the female urogenital tract. METHODS: We selected 102 healthy women from Yunnan Province as the research object, collected cervical exfoliation fluid, vaginal, urethral, and rectal swabs for microbial community analysis, and measured bacterial load, and related cytokine content. The link between HPV, microbiota, and inflammation was comprehensively evaluated using bioinformatics methods. FINDINGS: The impact of HPV infection on the microbial composition of different parts varies. We have identified several signature bacterial genera that respond to HPV infection in several detection sites, such as Corynebacterium, Lactobacillus, Campylobacter, and Cutibacterium have been detected in multiple sites, reflecting their potential significance in cross body sites HPV infection responses. There was a solid microbial interaction network between the cervix, vagina, and urethra. The interrelationships between inflammatory factors and different bacterial genera might also affect the immune system's response to HPV infection. INTERPRETATION: It might be an effective strategy to prevent and treat HPV infection by simultaneously understanding the correlation between the microbial changes in multiple parts of the female urogenital tract and rectum and HPV infection, and controlling the microbial network related to HPV infection in different parts.


Asunto(s)
Infecciones por Papillomavirus , Recto , Femenino , Humanos , China , Vagina/microbiología , Bacterias , ARN Ribosómico 16S , Papillomaviridae
18.
J Mater Chem B ; 12(7): 1905-1925, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38305576

RESUMEN

Hydrogels with multifunctional properties activated at specific times have gained significant attention in the biomedical field. As bacterial infections can cause severe complications that negatively impact wound repair, herein, we present the development of a stimuli-responsive, injectable, and in situ-forming hydrogel with antibacterial, self-healing, and drug-delivery properties. In this study, we prepared a Pluronic F-127 (PF127) and sodium alginate (SA)-based hydrogel that can be targeted to a specific tissue via injection. The PF127/SA hydrogel was incorporated with polymeric short-filaments (SFs) containing an anti-inflammatory drug - ketoprofen, and stimuli-responsive polydopamine (PDA) particles. The hydrogel, after injection, could be in situ gelated at the body temperature, showing great in vitro stability and self-healing ability after 4 h of incubation. The SFs and PDA improved the hydrogel injectability and compressive strength. The introduction of PDA significantly accelerated the KET release under near-infrared light exposure and extended its release validity period. The excellent composites' photo-thermal performance led to antibacterial activity against representative Gram-positive and Gram-negative bacteria, resulting in 99.9% E. coli and S. aureus eradication after 10 min of NIR light irradiation. In vitro, fibroblast L929 cell studies confirmed the materials' biocompatibility and paved the way toward further in vivo and clinical application of the system for chronic wound treatments.


Asunto(s)
Antibacterianos , Hidrogeles , Antibacterianos/farmacología , Hidrogeles/farmacología , Staphylococcus aureus , Escherichia coli , Bacterias Gramnegativas , Bacterias Grampositivas
19.
Heliyon ; 10(4): e26082, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38404812

RESUMEN

Background: Social isolation can be particularly challenging for individuals with high autistic traits who struggle with social interactions. The COVID-19 pandemic led to increased isolation, exacerbating stress for those who may have difficulty in connecting with others. This study aimed to explore the relationship between autistic traits and stress associated with social isolation. Methods: A sample of 1597 Chinese adults completed measures of autistic traits, the stress of social isolation, psychological inflexibility and core self-evaluation, during an epidemic prevention and control period of COVID-19 in Chongqing, China. Measures included the Autism-Spectrum Quotient, Coronavirus Stress Measure, Acceptance and Action Questionnaire-II, and Core Self-Evaluation Scale. Results: Autistic traits were positively correlated with the stress of social isolation, which was mediated by the chain effect of core self-evaluation and psychological inflexibility. individuals with high autistic traits reported significantly higher stress than individuals with low autistic traits. Limitations: This was a cross-sectional study, which limits causal inference. In addition, data were self-reported, which may cause methodological effects. Finally, this study was conducted during China's quarantine policy and external validation of the findings is required. Conclusions: Autistic traits are positively associated with the stress of social isolation. Autistic traits affected core self-evaluation first, and psychological inflexibility subsequently, leading to the stress of social isolation. individuals with high autistic traits tended to experience higher levels of stress during pandemic quarantines. The findings provide useful evidence for developing interventions and implementing preventive measures to reduce stress in individuals with high autistic traits and autism spectrum disorder.

20.
Mar Drugs ; 22(2)2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38393047

RESUMEN

Patients with ulcerative colitis (UC) have higher rates of depression. However, the mechanism of depression development remains unclear. The improvements of EPA and DHA on dextran sulfate sodium (DSS)-induced UC have been verified. Therefore, the present study mainly focused on the effects of EPA and DHA on UC-induced depression in C57BL/6 mice and the possible mechanisms involved. A forced swimming test and tail suspension experiment showed that EPA and DHA significantly improved DSS-induced depressive-like behavior. Further analysis demonstrated that EPA and DHA could significantly suppress the inflammation response of the gut and brain by regulating the NLRP3/ASC signal pathway. Moreover, intestine and brain barriers were maintained by enhancing ZO-1 and occludin expression. In addition, EPA and DHA also increased the serotonin (5-HT) concentration and synaptic proteins. Interestingly, EPA and DHA treatments increased the proportion of dominant bacteria, alpha diversity, and beta diversity. In conclusion, oral administration of EPA and DHA alleviated UC-induced depressive-like behavior in mice by modulating the inflammation, maintaining the mucosal and brain barriers, suppressing neuronal damage and reverting microbiota changes.


Asunto(s)
Colitis Ulcerosa , Humanos , Ratones , Animales , Sulfato de Dextran/toxicidad , Ratones Endogámicos C57BL , Colitis Ulcerosa/metabolismo , Transducción de Señal , Inflamación/metabolismo , Modelos Animales de Enfermedad , Colon/metabolismo
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