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The escalating worldwide prevalence of Crohn's disease (CD) among children and adolescents, coupled with a trend toward earlier onset, presents significant challenges for healthcare systems. Moreover, the chronicity of this condition imposes substantial individual burdens. Consequently, the principal objective of CD treatment revolves around rapid inducing remission. This study scrutinizes the impact of age, gender, initial disease localization, and therapy on the duration to achieve disease activity amelioration. Data from the Saxon Pediatric IBD Registry in Germany were analyzed over a period of 15 years. In addition to descriptive methods, logistic and linear regression analyses were conducted to identify correlations. Furthermore, survival analyses and Cox regressions were utilized to identify factors influencing the time to improvement in disease activity. These effects were expressed as Hazard Ratios (HR) with 95% confidence intervals. Data on the clinical course of 338 children and adolescents with CD were available in the registry. The analyses showed a significant correlation between a young age of onset and the severity of disease activity. It was evident that treatment with anti-TNF (Infliximab) was associated with a more favorable prognosis in terms of the time required for improvement in disease activity. Similarly, favorable outcomes were observed with the combination therapies of infliximab with enteral nutrition therapy and Infliximab with immunosuppressants.Conclusion: Our analysis of data from the Saxon Pediatric IBD Registry revealed that the timeframe for improvement of disease activity in pediatric Crohn's disease is influenced by several factors. Specifically, patient age, treatment modality, and initial site of inflammation were found to be significant factors. The study provides important findings that underline the need for individualized treatment.
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Elucidate the pathogenesis mechanism of post-stroke cognitive impairment (PSCI) can help to develop precision interventions. In this study, we established a mouse model of PSCI using the photochemical method, and behavioral tests including Y-maze and Novel object recognition task for accessing cognitive impairment were observed at week 2 post-stroke. Besides, synaptic plasticity, theta nerve oscillatory and the activity of glutamatergic neurons related to the ventral hippocampal-medial prefrontal glutamatergic neural pathway in the non-affected hemisphere (contralateral hemisphere to the lesion site) were observed. The result indicated the cognitive function declined at week 2 post-stroke. Synaptic plasticity, theta nerve oscillatory synchronization and the activity of glutamatergic neurons of the ventral hippocampal-medial prefrontal glutamatergic neural pathway in the non-affected hemisphere was down-regulated in the PSCI group compared to those of the SHAM group. Therefore we concluded that the declined function of the ventral hippocampal-medial prefrontal glutamatergic pathway in the non-affected hemisphere is a biomarker in the occurrence of cognitive dysfunction after stroke.
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The synthesis of novel water-soluble polymers with biodegradability is an effective way to mitigate their negative environmental impacts. In this study, semi-aromatic copolyester poly(butylene succinate-co-butylene terephthalate) (PBST) with exceptional biodegradability is used as the resin matrix. Anionic sodium 1-3-isophthalate-5-sulfonate (SIPA) is introduced as a fourth monomer to prepare random poly(butylene succinate-co-butylene terephthalate-co-butylene 5-sodiosulfoisophthalate) (PBSTS) copolyesters by melt copolymerization. The incorporation of ionic groups enhances the hydrophilicity and water absorption of the copolyesters, resulting in water-soluble materials that exhibit ionic and temperature responsivity. Furthermore, the ionized biodegradable copolyesters demonstrate distinct pH-dependent degradation, which is accelerated at pH = 5.5 and 8.5 but inhibited at pH = 7.2. Degradation assessments in simulated body fluids reveal that the PBSTS copolyesters exhibit significant degradation in gastric fluids at pH = 1.5 with minimal degradation in intestinal fluids at pH = 6.8 and in body fluids at pH = 7.0. This unique degradation performance highlights the potential of these materials for addressing the challenges associated with selective drug delivery and localized controlled release in the human body.
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Based on favorable outcomes and decreased propensity for lymph node and distant metastasis, multiple ground-glass nodules (GGNs) are now predominantly recognized as early-stage primary independent lung cancer. In this study, we discuss a case involving a patient with reoperative multifocal GGNs who was ultimately diagnosed with early multiple intrapulmonary metastases and multifocal primary lung cancers. This patient exhibited multisite epidermal growth factor receptor (EGFR) mutations, including the classical L858R, exon 19 deletion and the rare V834L variant. Despite a high tumor burden and the presence of various EGFR driver mutations, the patient experienced prolonged dormancy and exceptionally slow lesion growth, even without any systemic treatment. Our research indicates that the patient's immune response against the tumor remained robust throughout the disease course. Furthermore, we found that pathways associated with integrin-mediated cell extracellular matrix adhesion played a role in activating her innate immune responses and regulating tumor dormancy. Our findings suggest that the interplay between cancer cell mutations and the tumor microenvironment (TME) phenotype during tumor evolution contributed to this patient's prolonged survival. Integrating these aspects for lung tumor stratification is expected to improve predictions of growth potential and aid in clinical decision making.
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The integration of artificial intelligence (AI) algorithms into clinical practice holds immense potential to improve patient care, but widespread adoption still faces significant challenges, including interoperability issues. We propose a concept for the agile development of an IT platform to integrate AI-based applications into clinical workflows for a use case in ophthalmology.
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Inteligencia Artificial , Integración de Sistemas , Oftalmología , Sistemas de Apoyo a Decisiones Clínicas/organización & administración , Humanos , Registros Electrónicos de Salud , Algoritmos , Flujo de TrabajoRESUMEN
Current biofabrication strategies are limited in their ability to replicate native shape-to-function relationships, that are dependent on adequate biomimicry of macroscale shape as well as size and microscale spatial heterogeneity, within cell-laden hydrogels. In this study, a novel diffusion-based microfluidics platform is presented that meets these needs in a two-step process. In the first step, a hydrogel-precursor solution is dispersed into a continuous oil phase within the microfluidics tubing. By adjusting the dispersed and oil phase flow rates, the physical architecture of hydrogel-precursor phases can be adjusted to generate spherical and plug-like structures, as well as continuous meter-long hydrogel-precursor phases (up to 1.75 m). The second step involves the controlled introduction a small molecule-containing aqueous phase through a T-shaped tube connector to enable controlled small molecule diffusion across the interface of the aqueous phase and hydrogel-precursor. Application of this system is demonstrated by diffusing co-initiator sodium persulfate (SPS) into hydrogel-precursor solutions, where the controlled SPS diffusion into the hydrogel-precursor and subsequent photo-polymerization allows for the formation of unique radial stiffness patterns across the shape- and size-controlled hydrogels, as well as allowing the formation of hollow hydrogels with controllable internal architectures. Mesenchymal stromal cells are successfully encapsulated within hollow hydrogels and hydrogels containing radial stiffness gradient and found to respond to the heterogeneity in stiffness through the yes-associated protein mechano-regulator. Finally, breast cancer cells are found to phenotypically switch in response to stiffness gradients, causing a shift in their ability to aggregate, which may have implications for metastasis. The diffusion-based microfluidics thus finds application mimicking native shape-to-function relationship in the context of tissue engineering and provides a platform to further study the roles of micro- and macroscale architectural features that exist within native tissues.
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Hidrogeles , Microfluídica , Ingeniería de Tejidos , Hidrogeles/química , Humanos , Microfluídica/métodos , Microfluídica/instrumentación , Células Madre Mesenquimatosas/citologíaRESUMEN
The vinylene-linked covalent organic frameworks (viCOFs) have been generally synthesized in the presence of homogeneous catalysts such as KOH or trifluoroacetic acid. However, highly ordered viCOFs cannot always be obtained due to the uncommitted growth of viCOF layers in the homogeneous system with ubiquitous catalysts. Here, we propose a scalable protocol to restrict the growth of viCOFs along the two-dimensional (2D) plane by introducing a heterogeneous catalyst, polyoxometalates (POMs). With the unique Brønsted alkalinity and catalytic surface, POMs induce the growth of 2D viCOF layers along the surface of the catalytic substrate and restrain the generation of out-of-plane branches. Based on this protocol, six typical 2D viCOFs with high crystallinity and porosity were synthesized within a shorter reaction time as compared with the reported works using the common homogeneous catalysts for viCOF synthesis. On the basis of the density functional theory calculations and experimental results, a bottom intercalation growth pattern of viCOFs was revealed during the heterogeneous reaction. The unique growth pattern greatly promotes the orderly assembly of monomers, thus shortening the reaction time and improving the crystallinity of viCOFs. Furthermore, this heterogeneous catalysis strategy is suitable for the gram-scale preparation of 2D viCOFs. These results provide a novel avenue for the synthesis of high-quality viCOFs and may bring new insights into the synthetic methodology of COFs.
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OBJECTIVE: The FDA Adverse Event Reporting System (FAERS) was used to mine and evaluate adverse events (AEs) associated with cyclin-dependent kinase (CDK) 4/6 inhibitors, thereby providing a reference for clinical rational drug use. METHODS: AE data related to CDK4/6 inhibitors from the first quarter of 2015 to the first quarter of 2023 were acquired from FAERS, while the signal mining was processed using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. RESULTS: The number of AE reports for CDK4/6 inhibitors was, respectively, 132,494 for palbociclib, 56,151 for ribociclib, and 7,014 for abemaciclib. The corresponding numbers of AE signals were 319, 517, and 59, with the number of involved System Organ Class (SOC) being 23, 23, and 15, mainly involving blood and lymphatic system disorders, respiratory, thoracic and mediastinal disorders, hepatobiliary disorders, skin and subcutaneous tissue disorders, etc. CONCLUSION: CDK4/6 inhibitors could lead to pulmonary toxicity, myelosuppression, skin reactions, etc. Special attention should be paid to abemaciclib for interstitial lung disease (ILD), erythema multiforme, and thrombosis risk; ribociclib for cardiac toxicity, hepatotoxicity, and musculoskeletal toxicity; palbociclib for neurocognitive impairment and osteonecrosis of the jaw.
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BACKGROUND: Myopia is one of the most common eye diseases in children and adolescents worldwide, and scleral remodeling plays a role in myopia progression. However, the identity of the initiating factors and signaling pathways that induce myopia-associated scleral remodeling is still unclear. This study aimed to identify biomarkers of scleral remodeling to elucidate the pathogenesis of myopia. METHODS: The gene expression omnibus (GEO) and comparative toxicogenomics database (CTD) mining were used to identify the miRNA-mRNA regulatory network related to scleral remodeling in myopia. Real-time quantitative PCR (RT-qPCR), Western blot, immunofluorescence, H&E staining, Masson staining, and flow cytometry were used to detect the changes in the FOXO signaling pathway, fibrosis, apoptosis, cell cycle, and other related factors in scleral remodeling. RESULTS: miR-15b-5p/miR-379-3p can regulate the FOXO signaling pathway. Confirmatory studies confirmed that the axial length of the eye was significantly increased, the scleral thickness was thinner, the levels of miR-15b-5p, miR-379-3p, PTEN, p-PTEN, FOXO3a, cyclin-dependent kinase (CDK) inhibitor 1B (CDKN1B) were increased, and the levels of IGF1R were decreased in Len-induced myopia (LIM) group. CDK2, cyclin D1 (CCND1), and cell cycle block assessed by flow cytometry indicated G1/S cell cycle arrest in myopic sclera. The increase in BAX level and the decrease in BCL-2 level indicated enhanced apoptosis of the myopic sclera. In addition, we found that the levels of transforming growth factor-ß1 (TGF-ß1), collagen type 1 (COL-1), and α-smooth muscle actin (α-SMA) were decreased, suggesting scleral remodeling occurred in myopia. CONCLUSIONS: miR-15b-5p/miR-379-3p can regulate the scleral cell cycle and apoptosis through the IGF1R/PTEN/FOXO signaling pathway, thereby promoting scleral remodeling in myopia progression.
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Apoptosis , Ciclo Celular , Factores de Transcripción Forkhead , MicroARNs , Miopía , Esclerótica , Transducción de Señal , Animales , Apoptosis/genética , Secuencia de Bases , Ciclo Celular/genética , Modelos Animales de Enfermedad , Factores de Transcripción Forkhead/metabolismo , Factores de Transcripción Forkhead/genética , MicroARNs/genética , MicroARNs/metabolismo , Miopía/genética , Miopía/patología , Miopía/metabolismo , Esclerótica/patología , Esclerótica/metabolismoRESUMEN
The extracellular matrix (ECM) shapes the stem cell fate during differentiation by exerting relevant biophysical cues. However, the mechanism of stem cell fate decisions in response to ECM-backed complex biophysical cues has not been fully understood due to the lack of versatile ECMs. Here, we designed two versatile ECMs using colloidal self-assembly technology to probe the mechanisms of their effects on mechanotransduction and stem cell fate regulation. Binary colloidal crystals (BCC) with a hexagonally close-packed structure, composed of silica (5 µm) and polystyrene (0.4 µm) particles as well as a polydimethylsiloxane-embedded BCC (BCCP), were fabricated. They have defined surface chemistry, roughness, stiffness, ion release, and protein adsorption properties, which can modulate the cell adhesion, proliferation, and differentiation of human adipose-derived stem cells (hASCs). On the BCC, hASCs preferred osteogenesis at an early stage but showed a higher tendency toward adipogenesis at later stages. In contrast, the results of BCCP diverged from those of BCC, suggesting a unique regulation of ECM-dependent mechanotransduction. The BCC-mediated cell adhesion reduced the size of the focal adhesion complex, accompanying an ordered spatial organization and cytoskeletal rearrangement. This morphological restriction led to the modulation of mechanosensitive transcription factors, such as c-FOS, the enrichment of transcripts in specific signaling pathways such as PI3K/AKT, and the activation of the Hippo signaling pathway. Epigenetic analyses showed changes in histone modifications across different substrates, suggesting that chromatin remodeling participated in BCC-mediated mechanotransduction. This study demonstrates that BCCs are versatile artificial ECMs that can regulate human stem cells' fate through unique biological signaling, which is beneficial in biomaterial design and stem cell engineering.
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Diferenciación Celular , Coloides , Epigénesis Genética , Células Madre Mesenquimatosas , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Coloides/química , Dimetilpolisiloxanos/química , Dimetilpolisiloxanos/farmacología , Adhesión Celular/efectos de los fármacos , Mecanotransducción Celular/efectos de los fármacos , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Dióxido de Silicio/química , Poliestirenos/química , Proliferación Celular/efectos de los fármacos , Osteogénesis/efectos de los fármacosRESUMEN
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder leading to cognitive decline. Excessive cytosolic calcium (Ca2+) accumulation plays a critical role in the pathogenesis of AD since it activates the NOD-like receptor family, pyrin domain containing 3 (NLRP3), switches the endoplasmic reticulum (ER) unfolded protein response (UPR) toward proapoptotic signaling and promotes Aß seeding. Herein, a liposomal nanodrug (felodipine@LND) is developed incorporating a calcium channel antagonist felodipine for Alzheimer's disease treatment through a low-intensity pulse ultrasound (LIPUS) irradiation-assisted blood brain barrier (BBB)-crossing drug delivery. The multifunctional felodipine@LND is effectively delivered to diseased brain through applying a LIPUS irradiation to the skull, which resulted in a series of positive effects against AD. Markedly, the nanodrug treatment switched the ER UPR toward antioxidant signaling, prevented the surface translocation of ER calreticulin (CALR) in microglia, and inhibited the NLRP3 activation and Aß seeding. In addition, it promoted the degradation of damaged mitochondria via mitophagy, thereby inhibiting the neuronal apoptosis. Therefore, the anxiety-like behavior and cognitive impairment of 5xFAD mice with AD is significantly ameliorated, which manifested the potential of LIPUS - assisted BBB-crossing delivery of felodipine@LND to serve as a paradigm for AD therapy based on the well-recognized clinically available felodipine.
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Mycotoxins are secondary products produced primarily by fungi and are pathogens of animals and cereals, not only affecting agriculture and the food industry but also causing great economic losses. The development of rapid and sensitive methods for the detection of mycotoxins in food is of great significance for livelihood issues. This study employed an amino-functionalized zirconium luminescent metal-organic framework (LOF) (i.e., UiO-66-NH2). Click chemistry was utilized to assemble UiO-66-NH2 in a controlled manner, generating LOF assemblies to serve as probes for fluorescence-linked immunoassays. The proposed fluoroimmunoassay method for Zearalenone (ZEN) and Fumonisin B1 (FB1) detection based on the UiO-66-NH2 assembled probe (CLICK-FLISA) afforded a linear response range of 1-20 µmol/L for ZEN, 20 µmol/L for FB1, and a very low detection limit (0.048-0.065 µmol/L for ZEN; 0.048-0.065 µmol/L for FB1). These satisfying results demonstrate promising applications for on-site quick testing in practical sample analysis. Moreover, the amino functionalization may also serve as a modification strategy to design luminescent sensors for other food contaminants.
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Fumonisinas , Estructuras Metalorgánicas , Zea mays , Zearalenona , Fumonisinas/análisis , Zearalenona/análisis , Estructuras Metalorgánicas/química , Zea mays/química , Química Clic , Fluoroinmunoensayo/métodos , Técnicas Biosensibles , Contaminación de Alimentos/análisis , Límite de Detección , Micotoxinas/análisisRESUMEN
Bone cancer pain (BCP) is a complex clinical challenge, with current treatments often falling short of providing adequate relief. Remimazolam, a benzodiazepine receptor agonist recognized for its anxiolytic effects, has emerged as a potential agent in managing BCP. This study explores the analgesic properties of remimazolam and its interaction with the translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, in spinal astrocytes. In the context of BCP, previous research has indicated that TSPO expression in spinal astrocytes may serve a protective regulatory function in neuropathic pain models. Building on this, the BCP mice received various doses of remimazolam on the 15th day post-inoculation, and pain behavior was assessed over time. The results showed that BCP induced an upregulation of TSPO and astrocyte activation in the spinal dorsal horn, alongside increased extracellular signal-regulated kinase (ERK) signaling and inflammatory cytokine expression. Remimazolam administration resulted in a dose-dependent reduction of pain behaviors, which corresponded with a decrease in both ERK pathway activation and inflammatory factor expression. This suggests that remimazolam's analgesic effects are mediated through its action as a TSPO agonist, leading to the attenuation of neuroinflammation and pain signaling pathways. Importantly, the analgesic effects of remimazolam were reversed by the TSPO antagonist PK11195, underscoring the pivotal role of TSPO in the drug's mechanism of action. This reversal also reinstated the heightened levels of ERK activity and inflammatory mediators, further confirming the involvement of TSPO in the modulation of these pain-related processes. These findings open new avenues for the therapeutic management of bone cancer pain, positioning remimazolam as a promising candidate for further investigation and development.
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Astrocitos , Neoplasias Óseas , Dolor en Cáncer , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Ratones , Dolor en Cáncer/tratamiento farmacológico , Dolor en Cáncer/metabolismo , Neoplasias Óseas/metabolismo , Neoplasias Óseas/complicaciones , Neoplasias Óseas/tratamiento farmacológico , Benzodiazepinas/farmacología , Benzodiazepinas/uso terapéutico , Femenino , Receptores de GABA/metabolismo , Analgésicos/farmacología , Analgésicos/uso terapéutico , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacosRESUMEN
Radiation-induced lung injury (RILI) is a severe complication arising from thoracic tumor radiotherapy, which constrains the possibility of increasing radiation dosage. Current RILI therapies provide only limited relief and may result in undesirable side effects. Therefore, there is an urgent demand for effective and low-toxicity treatments for RILI. Macrophages play a pivotal role in RILI, promoting inflammation in the initial stages and facilitating fibrosis in the later stages. Sodium clodronate, a bisphosphonate, can induce macrophage apoptosis when encapsulated in liposomes. In this study, we explored the potential of liposomal sodium clodronate (LC) as a specific agent for depleting macrophages to alleviate acute RILI. We assessed the impact of LC on macrophage consumption both in vitro and in vivo. In a mouse model of acute RILI, LC treatment group led to a reduction in alveolar macrophage counts, mitigated lung injury severity, and lowered levels of pro-inflammatory cytokines in both plasma and bronchoalveolar lavage fluid. Additionally, we further elucidated the specific effects and mechanism of LC on macrophages in vitro. Alveolar macrophages MHS cells were subjected to varying concentrations of LC (0, 50, 100, 200 µg/ml), and the results demonstrated its dose-dependent inhibition of cell proliferation and induction of apoptosis. Moreover, LC decreased the secretion of pro-inflammatory cytokines, including IL-1ß, IL-6, and TNF-α. Conditioned media from LC-treated macrophages protected alveolar epithelial cells MLE-12 from radiation-induced damage, as demonstrated by reduced apoptosis and DNA damage. These findings imply that LC-mediated macrophage depletion may present a promising therapeutic strategy for alleviating radiation-induced lung injury.
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Introduction: Obtaining real-world data from routine clinical care is of growing interest for scientific research and personalized medicine. Despite the abundance of medical data across various facilities - including hospitals, outpatient clinics, and physician practices - the intersectoral exchange of information remains largely hindered due to differences in data structure, content, and adherence to data protection regulations. In response to this challenge, the Medical Informatics Initiative (MII) was launched in Germany, focusing initially on university hospitals to foster the exchange and utilization of real-world data through the development of standardized methods and tools, including the creation of a common core dataset. Our aim, as part of the Medical Informatics Research Hub in Saxony (MiHUBx), is to extend the MII concepts to non-university healthcare providers in a more seamless manner to enable the exchange of real-world data among intersectoral medical sites. Methods: We investigated what services are needed to facilitate the provision of harmonized real-world data for cross-site research. On this basis, we designed a Service Platform Prototype that hosts services for data harmonization, adhering to the globally recognized Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) international standard communication format and the Observational Medical Outcomes Partnership (OMOP) common data model (CDM). Leveraging these standards, we implemented additional services facilitating data utilization, exchange and analysis. Throughout the development phase, we collaborated with an interdisciplinary team of experts from the fields of system administration, software engineering and technology acceptance to ensure that the solution is sustainable and reusable in the long term. Results: We have developed the pre-built packages "ResearchData-to-FHIR," "FHIR-to-OMOP," and "Addons," which provide the services for data harmonization and provision of project-related real-world data in both the FHIR MII Core dataset format (CDS) and the OMOP CDM format as well as utilization and a Service Platform Prototype to streamline data management and use. Conclusion: Our development shows a possible approach to extend the MII concepts to non-university healthcare providers to enable cross-site research on real-world data. Our Service Platform Prototype can thus pave the way for intersectoral data sharing, federated analysis, and provision of SMART-on-FHIR applications to support clinical decision making.
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Background: Circulating tumor DNA (ctDNA) is a potential biomarker not only capable of monitoring the treatment response during neoadjuvant therapy (NAT) or rescue therapy, but also identifying minimal residual disease (MRD) and detecting early relapses after primary treatment. However, it remains uncertain whether the detection of ctDNA at diagnosis, before any treatment, can predict the prognosis for patients with early breast cancer. The objective of our study was to evaluate the predictive value of baseline ctDNA for prognosis in patients with early breast cancer. Methods: A total of 90 patients with early breast cancer and 24 healthy women were recruited between August 2016 and October 2016. Peripheral blood samples were collected from patients at diagnosis, before any treatment. Blood samples were processed and subjected to targeted deep sequencing with a next-generation sequencing (NGS) panel of 1,021 cancer-related genes. The recurrence-free survival (RFS) and invasive disease-free survival (iDFS) were reported. Results: The 90 patients with breast cancer included 6 patients with ductal carcinoma in situ (DCIS) and 84 patients with invasive breast cancer. Within the cohort of patients with invasive breast cancer, ctDNA were detected in 57 patients, with a ctDNA detection rate of 67.9%. Meanwhile, no ctDNA was detected in DCIS patients. Among 84 patients with invasive breast cancer, patients with high-level ctDNA had a significantly lower RFS compared to patients with low-level ctDNA (log-rank P=0.0036). Conclusions: Our study suggested that ctDNA at diagnosis, before any treatment, could potentially serve as a biomarker to predict the prognosis for patients with early breast cancer. However, further follow-up and more studies with large sample sizes are required to confirm these findings.
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OBJECTIVE: To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer. METHODS: The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo. RESULTS: Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G0/G1 phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05). CONCLUSION: Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.
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Neurofeedback, a non-invasive intervention, has been increasingly used as a potential treatment for major depressive disorders. However, the effectiveness of neurofeedback in alleviating depressive symptoms remains uncertain. To address this gap, we conducted a comprehensive meta-analysis to evaluate the efficacy of neurofeedback as a treatment for major depressive disorders. We conducted a comprehensive meta-analysis of 22 studies investigating the effects of neurofeedback interventions on depression symptoms, neurophysiological outcomes, and neuropsychological function. Our analysis included the calculation of Hedges' g effect sizes and explored various moderators like intervention settings, study designs, and demographics. Our findings revealed that neurofeedback intervention had a significant impact on depression symptoms (Hedges' g = -0.600) and neurophysiological outcomes (Hedges' g = -0.726). We also observed a moderate effect size for neurofeedback intervention on neuropsychological function (Hedges' g = -0.418). As expected, we observed that longer intervention length was associated with better outcomes for depressive symptoms (ß = -4.36, P < 0.001) and neuropsychological function (ß = -2.89, P = 0.003). Surprisingly, we found that shorter neurofeedback sessions were associated with improvements in neurophysiological outcomes (ß = 3.34, P < 0.001). Our meta-analysis provides compelling evidence that neurofeedback holds promising potential as a non-pharmacological intervention option for effectively improving depressive symptoms, neurophysiological outcomes, and neuropsychological function in individuals with major depressive disorders.
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Trastorno Depresivo Mayor , Neurorretroalimentación , Neurorretroalimentación/métodos , Humanos , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/fisiopatología , Resultado del Tratamiento , Electroencefalografía/métodosRESUMEN
Organizational resilience is a key concept in the study of sustainable corporate growth and indicates an organization's capacity to recover from adversity. It plays a crucial role in responding to uncertain crises. In recent years, academic interest in organizational resilience has increasingly gained prominence. This research uses CiteSpace and VOSviewer to provide a thorough visual analysis of pertinent international literature based on 342 pieces of closely linked literature about organizational resilience. The findings suggest that organizational resilience research is currently experiencing a development phase. Within this field, there is a substantial number of scholars involved, with the most prolific among them including Aleksic Aleksandar, Prayag Girish, and Griffiths Andrew. The networks of collaboration among these authors, nevertheless, are very scattered. Co-citation network research reveals the academics with the biggest sway in the field. Organizational resilience, conservation of resources theory, crisis management, corporate social responsibility, and emergency management are identified as research hotspots within the keyword co-citation network. Furthermore, to determine which countries and regions are the most influential, this study has created a cooperative network among them. China, the United States, and England are the top three nations with articles published. Not only are the highly cited journals respected in the management sector, but they also showcase noteworthy research accomplishments within the field. The purpose of this study is to investigate potential avenues for future research and offer helpful sources for choosing research subjects and developing theoretical frameworks in this area. The analysis is highly valuable as a reference for research on organizational resilience in different settings in the future.