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1.
Chem Biol Interact ; 403: 111220, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39222901

RESUMEN

Long-term hyperuricemia can induce kidney damage, clinically referred to as hyperuricemic nephropathy (HN), which is characterized by renal fibrosis, inflammation, and oxidative stress. However, currently used uric acid-lowering drugs are not capable of protecting the kidneys from damage. Therefore, uric acid-lowering drugs that can also protect the kidneys are urgently needed. In this study, we first discovered that salinomycin, an antibiotic, can regulate uric acid homeostasis and ameliorate kidney damage in mice with HN. Mechanistically, salinomycin inhibited serum and hepatic xanthine oxidase (XOD) activities and downregulated renal urate transporter 1 (URAT1) expression and transport activity, thus exerting uric acid-lowering effects in mice with HN. Furthermore, we found that salinomycin promoted p-NRF2 Ser40 expression, resulting in increased nuclear translocation of NRF2 and activation of NRF2. More importantly, salinomycin affected the gut microbiota and promoted the generation of short-chain fatty acids (SCFAs) in mice with HN. In conclusion, our results revealed that salinomycin maintains uric acid homeostasis and alleviates kidney injury in mice with HN by multiple mechanisms, suggesting that salinomycin might be a desirable candidate for HN treatment in the clinic.

2.
Zhongguo Zhong Yao Za Zhi ; 49(16): 4499-4509, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39307786

RESUMEN

This study explores the effects and mechanisms of Modified Xiaoyao Powder on the intestinal barrier and intestinal flora in mice with metabolic associated fatty liver disease(MAFLD) based on the " gut-liver axis". Sixty male C57BL/6 mice were randomly divided into the normal group, model group, bifidobacterium tetrad tablet group(SQ), and Modified Xiaoyao Powder groups with low,medium and high doses(XL, XM, XH), with 10 mice in each group. All the mice were administrated with a high-fat diet to build the MAFLD model except the normal group and then treated with related drugs for 12 weeks. Body mass, liver wet weight, and liver index were detected. Serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), total cholesterol(TC), triacylglycerol(TG), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C), and lipopolysaccharide(LPS)levels were detected using the biochemical kits. The contents of tumor necrosis factor-α(TNF-α) and interleukin(IL-6) in the liver were tested simultaneously. The morphological changes of the liver and intestine were observed using hematoxylin-eosin(HE) staining and oil red O staining. The goblet cells in the ileum were detected by periodic acid Schiff and alcian blue stain(AB-PAS) staining.The expression of zonula occludens-1(ZO-1), recombinant occludin(occludin), and recombinant claudin 1(claudin-1) in ileum and colon were detected by immunohistochemistry and Western blot. The changes of intestinal flora in mice were analyzed by 16S rRNA gene sequencing. The results showed that compared with the normal group, body weight, liver wet weight and liver index in the model group increased. The contents of TC, TG, ALT, AST, LDL-C, and LPS in the serum of the model group increased, while HDL-C decreased. Meanwhile, the contents of TNF-α and IL-6 in liver tissue increased and liver lipid accumulation increased, indicating successful model induction. Compared with the model group, body weight, liver wet weight, and liver index were decreased in XM,XH groups and SQ group. Serum levels of TC, TG, LDL-C, ALT and AST in XM group and SQ group were significantly decreased,and HDL-C levels were increased. The levels of IL-6, TNF-α in liver tissue and serum LPS in the XL, XM groups and SQ group were significantly decreased. The protein expression of claudin-1, occludin and ZO-1 in XL, XM groups and SQ group were increased. The analysis of intestinal flora showed that compared with the model group, Modified Xiaoyao Powder with a medium dose could significantly improve the richness and diversity of intestinal flora in mice. At the phylum level, the Firmicutes/Bacteroidetes(F/B) ratio decreased; at the genus level, Lactobacillus, Brautella, Bacteroides, and Ackermannia increased, while Prevotella, Desulfovibrio and Turicibacter decreased. The main differential species were Odorbacteraceaeae and Peptostreptococcaceae. In conclusion, Modified Xiaoyao Powder could inhibit inflammation, regulate intestinal flora homeostasis, and promote the repair of the intestinal mucosal barrier in mice with MAFLD.


Asunto(s)
Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Hígado , Ratones Endogámicos C57BL , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Masculino , Ratones , Microbioma Gastrointestinal/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Polvos , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Humanos , Alanina Transaminasa/metabolismo , Aspartato Aminotransferasas/metabolismo , Ocludina/metabolismo , Ocludina/genética , Hígado Graso/tratamiento farmacológico , Hígado Graso/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Proteína de la Zonula Occludens-1/metabolismo , Proteína de la Zonula Occludens-1/genética , Triglicéridos/metabolismo
4.
J Adv Res ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39243942

RESUMEN

INTRODUCTION: Brain organoids are believed to be able to regenerate impaired neural circuits and reinstate brain functionality. The neuronal activity of organoids is considered a crucial factor for restoring host function after implantation. However, the optimal stage of brain organoid post-transplantation has not yet been established. External electrical signal plays a crucial role in the physiology and development of a majority of human tissues. However, whether electrical input modulates the development of brain organoids, making them ideal transplant donors, is elusive. METHODS: Bioelectricity was input into cortical organoids by electrical stimulation (ES) with a multi-electrode array (MEA) to obtain a better-transplanted candidate with better viability and maturity, realizing structural-functional integration with the host brain. RESULTS: We found that electrical stimulation facilitated the differentiation and maturation of organoids, displaying well-defined cortical plates and robust functional electrophysiology, which was probably mediated via the pathway of calcium-calmodulin (CaM) dependent protein kinase II (CAMK II)-protein kinase A (PKA)-cyclic-AMP response binding protein (pCREB). The ES-pretreated D40 organoids displayed superior cell viability and higher cell maturity, and were selected to transplant into the damaged primary sensory cortex (S1) of host. The enhanced maturation was exhibited within grafts after transplantation, including synapses and complex functional activities. Moreover, structural-functional integration between grafts and host was observed, conducive to strengthening functional connectivity and restoring the function of the host injury. CONCLUSION: Our findings supported that electrical stimulation could promote the development of cortical organoids. ES-pretreated organoids were better-transplanted donors for strengthening connectivity between grafts and host. Our work presented a new physical approach to regulating organoids, potentially providing a novel translational strategy for functional recovery after brain injury. In the future, the development of 3D flexible electrodes is anticipated to overcome the drawbacks of 2D planar MEA, promisingly achieving multimodal stimulation and long-term recordings of brain organoids.

5.
J Lipid Res ; 65(9): 100626, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39173829

RESUMEN

Atherosclerotic cardiovascular disease is closely correlated with elevated low density lipoprotein-cholesterol. In feeding state, glucose and insulin activate mammalian target of rapamycin 1 that phosphorylates the deubiquitylase ubiquitin-specific peptidase 20 (USP20). USP20 then stabilizes HMG-CoA reductase, thereby increasing lipid biosynthesis. In this study, we applied clinically approved lipid nanoparticles to encapsulate the siRNA targeting Usp20. We demonstrated that silencing of hepatic Usp20 by siRNA decreased body weight, improved insulin sensitivity, and increased energy expenditure through elevating UCP1. In Ldlr-/- mice, silencing Usp20 by siRNA decreased lipid levels and prevented atherosclerosis. This study suggests that the RNAi-based therapy targeting hepatic Usp20 has a translational potential to treat metabolic disease.

6.
Nat Commun ; 15(1): 6557, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095346

RESUMEN

Gene-gene interactions are crucial to the control of sub-cellular processes but our understanding of their stochastic dynamics is hindered by the lack of simulation methods that can accurately and efficiently predict how the distributions of gene product numbers vary across parameter space. To overcome these difficulties, here we present Holimap (high-order linear-mapping approximation), an approach that approximates the protein or mRNA number distributions of a complex gene regulatory network by the distributions of a much simpler reaction system. We demonstrate Holimap's computational advantages over conventional methods by applying it to predict the stochastic time-dependent dynamics of various gene networks, including transcriptional networks ranging from simple autoregulatory loops to complex randomly connected networks, post-transcriptional networks, and post-translational networks. Holimap is ideally suited to study how the intricate network of gene-gene interactions results in precise coordination and control of gene expression.


Asunto(s)
Redes Reguladoras de Genes , Procesos Estocásticos , Modelos Genéticos , Simulación por Computador , Algoritmos , Regulación de la Expresión Génica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Biología Computacional/métodos
7.
MedComm (2020) ; 5(8): e662, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39144468

RESUMEN

Maturation of the secondary antibody repertoire requires class-switch recombination (CSR), which switches IgM to other immunoglobulins (Igs), and somatic hypermutation, which promotes the production of high-affinity antibodies. Following immune response or infection within the body, activation of T cell-dependent and T cell-independent antigens triggers the activation of activation-induced cytidine deaminase, initiating the CSR process. CSR has the capacity to modify the functional properties of antibodies, thereby contributing to the adaptive immune response in the organism. Ig CSR defects, characterized by an abnormal relative frequency of Ig isotypes, represent a rare form of primary immunodeficiency. Elucidating the molecular basis of Ig diversification is essential for a better understanding of diseases related to Ig CSR defects and could provide clues for clinical diagnosis and therapeutic approaches. Here, we review the most recent insights on the diversification of five Ig isotypes and choose several classic diseases, including hyper-IgM syndrome, Waldenström macroglobulinemia, hyper-IgD syndrome, selective IgA deficiency, hyper-IgE syndrome, multiple myeloma, and Burkitt lymphoma, to illustrate the mechanism of Ig CSR deficiency. The investigation into the underlying mechanism of Ig CSR holds significant potential for the advancement of increasingly precise diagnostic and therapeutic approaches.

8.
Front Neurosci ; 18: 1437668, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39145292

RESUMEN

Hereditary spastic paraplegia (HSP) is a heterogeneous group of neurological disorders that are characterized by progressive spasticity and weakness in the lower limbs. SPG26 is a complicated form of HSP, which includes not only weakness in the lower limbs, but also cognitive impairment, developmental delay, cerebellar ataxia, dysarthria, and peripheral neuropathy, and is caused by biallelic mutations in the B4GALNT1 (beta-1,4-N-acetylgalactosaminyltransferase 1) gene. The B4GALNT1 gene encodes ganglioside GM2/GD2 synthase (GM2S), which catalyzes the transfer of N-acetylgalactosamine to lactosylceramide, GM3, and GD3 to generate GA2, GM2, and GD2, respectively. The present study attempted to characterize a novel B4GALNT1 variant (NM_001478.5:c.937G>A p.Asp313Asn) detected in a patient with progressive multi-system neurodegeneration as well as deleterious variants found in the general population in Japan. Peripheral blood T cells from our patient lacked the ability for activation-induced ganglioside expression assessed by cell surface cholera toxin binding. Structural predictions suggested that the amino acid substitution, p.Asp313Asn, impaired binding to the donor substrate UDP-GalNAc. An in vitro enzyme assay demonstrated that the variant protein did not exhibit GM2S activity, leading to the diagnosis of HSP26. This is the first case diagnosed with SPG26 in Japan. We then extracted 10 novel missense variants of B4GALNT1 from the whole-genome reference panel jMorp (8.3KJPN) of the Tohoku medical megabank organization, which were predicted to be deleterious by Polyphen-2 and SIFT programs. We performed a functional evaluation of these variants and demonstrated that many showed perturbed subcellular localization. Five of these variants exhibited no or significantly decreased GM2S activity with less than 10% activity of the wild-type protein, indicating that they are carrier variants for HSP26. These results provide the basis for molecular analyses of B4GALNT1 variants present in the Japanese population and will help improve the molecular diagnosis of patients suspected of having HSP.

9.
Huan Jing Ke Xue ; 45(8): 4600-4609, 2024 Aug 08.
Artículo en Chino | MEDLINE | ID: mdl-39168679

RESUMEN

Microplastics pose a serious ecological threat to rivers in China, and the construction of a large number of dams has complicated this problem. Ten dams of the Shaying River were chosen to investigate the abundance and composition of microplastics in surface water and sediments of the reservoir and upstream river. Ecological risk was evaluated using species sensitive distribution (SSD) and pollution load index (PLI). The results showed that the Shaying River was exposed to a severe risk of microplastics from upstream to downstream. The construction of dams did not significantly affect the distribution of microplastics in the river. River sediments became a sink for microplastics in the surface water; however, the ecological risk posed by microplastics in the surface water was greater, and the comparison of the two assessment methods showed that the species sensitivity distribution assessment better reflected the accumulation and feeding behavior of organisms to pollutants compared to the pollution load index.


Asunto(s)
Monitoreo del Ambiente , Microplásticos , Ríos , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/análisis , China , Medición de Riesgo , Microplásticos/análisis , Sedimentos Geológicos/química
10.
Brain Commun ; 6(4): fcae263, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39171204

RESUMEN

Evidence indicates that the default mode network (DMN) plays a crucial role in the neuropathology of major depressive disorder (MDD). However, the neural signatures of DMN subsystems in MDD after low resistance Thought Induction Psychotherapy (TIP) remain incompletely understood. We collected functional magnetic resonance imaging data from 20 first-episode, drug-naive MDD and 20 healthy controls (HCs). The DMN was segmented into three subsystems and seed-based functional connectivity (FC) was computed. After 6-week treatment, the significantly reduced FCs with the medial temporal lobe memory subsystem in MDD at baseline were enhanced and were comparable to that in HCs. Changed Hamilton Depression Rating Scale scores were significantly related with changed FC between the posterior cingulate cortex (PCC) and the right precuneus (PCUN). Further, changed serotonin 5-hydroxytryptamine levels were significantly correlated with changed FCs between the PCC and the left PCUN, between the posterior inferior parietal lobule and the left inferior temporal gyrus, and between the retrosplenial cortex and the right inferior frontal gyrus, opercular part. Finally, the support vector machine obtained an accuracy of 67.5% to distinguish between MDD at baseline and HCs. These findings may deepen our understanding of the neural basis of the effects of TIP on DMN subsystems in MDD.

11.
Microsyst Nanoeng ; 10: 107, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39101004

RESUMEN

With the increasing development of intelligent robots and wearable electronics, the demand for high-performance flexible energy storage devices is drastically increasing. In this study, flexible symmetric microsupercapacitors (MSCs) that could operate in a wide working voltage window were developed by combining laser-direct-writing graphene (LG) electrodes with a phosphoric acid-nonionic surfactant liquid crystal (PA-NI LC) gel electrolyte. To increase the flexibility and enhance the conformal ability of the MSC devices to anisotropic surfaces, after the interdigitated LG formed on the polyimide (PI) film surface, the devices were further transferred onto a flexible, stretchable and transparent polydimethylsiloxane (PDMS) substrate; this substrate displayed favorable flexibility and mechanical characteristics in the bending test. Furthermore, the electrochemical performances of the symmetric MSCs with various electrode widths (300, 400, 500 and 600 µm) were evaluated. The findings revealed that symmetric MSC devices could operate in a large voltage range (0-1.5 V); additionally, the device with a 300 µm electrode width (MSC-300) exhibited the largest areal capacitance of 2.3 mF cm-2 at 0.07 mA cm-2 and an areal (volumetric) energy density of 0.72 µWh cm- 2 (0.36 mWh cm- 3) at 55.07 µW cm-2 (27.54 mW cm-3), along with favorable mechanical and cycling stability. After charging for ~20 s, two MSC-300 devices connected in series could supply energy to a calculator to operate for ~130 s, showing its practical application potential as an energy storage device. Moreover, the device displayed favorable reversibility, stability and durability. After 12 months of aging in air at room temperature, its electrochemical performance was not altered, and after charging-discharging measurements for 5000 cycles at 0.07 mA cm-2, ~93.6% of the areal capacitance was still retained; these results demonstrated its practical long-term application potential as an energy storage device.

12.
Microsyst Nanoeng ; 10: 102, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39045232

RESUMEN

With the rapid development of various fields, including aerospace, industrial measurement and control, and medical monitoring, the need to quantify flow velocity measurements is increasing. It is difficult for traditional flow velocity sensors to fulfill accuracy requirements for velocity measurements due to their small ranges, susceptibility to environmental impacts, and instability. Herein, to optimize sensor performance, a flexible microelectromechanical system (MEMS) thermal flow sensor is proposed that combines the working principles of thermal loss and thermal temperature difference and utilizes a flexible cavity substrate made of a low-thermal-conductivity polyimide/SiO2 (PI/SiO2) composite porous film to broaden the measurement range and improve the sensitivity. The measurement results show that the maximum measurable flow velocity can reach 30 m/s with a resolution of 5.4 mm/s. The average sensitivities of the sensor are 59.49 mV/(m s-1) in the medium-to-low wind velocity range of 0-2 m/s and 467.31 mV/(m s-1) in the wind velocity range of 2-30 m/s. The sensor proposed in this work can enable new applications of flexible flow sensors and wearable devices.

13.
World J Clin Cases ; 12(18): 3515-3528, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38983402

RESUMEN

BACKGROUND: Iron deficiency anemia (IDA) is a prevalent nutritional disorder during pregnancy. Clinical studies indicate that incorporating Chinese patent medicines (CPMs) with oral iron (OI) in treating IDA in pregnancy can reduce adverse effects and improve clinical outcomes. Nonetheless, the comparative efficacy of different CPMs remains unclear. AIM: To assess the safety and effectiveness of different CPMs for treating IDA during pregnancy using network meta-analysis. METHODS: We conducted a search for randomized controlled trials (RCTs) that combined CPM and OI for IDA treatment in pregnancy, spanning from 2013 to the present. Data analysis was performed using Rev Man 5.3 and Stata 14.0 on literature that satisfied the quality criteria. RESULTS: The analysis included 45 RCTs, encompassing 4422 pregnant patients with IDA. Six CPMs were examined, including Shengxuebao Mixture, Shengxuening Tablets (SXN), Yiqi Weixue CPMs (YQWX), Jianpi Shengxue CPMs (JPSX), Yiqi Buxue Tablets, and Compound Hongyi Buxue Oral Liquid (FFHY). Findings indicated that FFHY + OI significantly improved the clinical effective rate. SXN + OI was most effective in boosting red blood cells counts and hemoglobin levels. YQWX + OI showed superior results in improving serum ferritin, and SXN + OI was most effective in increasing serum iron levels. JPSX + OI was optimal in reducing adverse pregnancy outcomes, while YQBX + OI effectively minimized adverse events. A cluster analysis suggested that SXN + OI could be the potentially optimal therapeutic regimen for IDA in pregnancy. CONCLUSION: This study demonstrates that the combination of OI with CPMs offers better outcomes than OI alone. Based on clinical efficacy and other measured outcomes, SXN + OI emerges as the most effective treatment modality for improving the health of pregnant patients with IDA.

14.
Adv Mater ; : e2404659, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38870958

RESUMEN

Single-atom electrocatalysts (SACs) are a class of promising materials for driving electrochemical energy conversion reactions due to their intrinsic advantages, including maximum metal utilization, well-defined active structures, and strong interface effects. However, SACs have not reached full commercialization for broad industrial applications. This review summarizes recent research achievements in the design of SACs for crucial electrocatalytic reactions on their active sites, coordination, and substrates, as well as the synthesis methods. The key challenges facing SACs in activity, selectivity, stability, and scalability, are highlighted. Furthermore, it is pointed out the new strategies to address these challenges including increasing intrinsic activity of metal sites, enhancing the utilization of metal sites, improving the stability, optimizing the local environment, developing new fabrication techniques, leveraging insights from theoretical studies, and expanding potential applications. Finally, the views are offered on the future direction of single-atom electrocatalysis toward commercialization.

15.
Oral Dis ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38923332

RESUMEN

OBJECTIVES: Porphyromonas gingivalis-LPS regulated bone metabolism by triggering dysfunction of osteoblasts directly, and affecting activity of osteoclasts through intracellular communication. Exosome, as the mediator of intercellular communication, was important vesicle to regulate osteogenesis and osteoclastogenesis. This research was designed for investigating the mechanism of BMSCs-EXO in modulating osteoclastic activity under the P. gingivalis-LPS. MATERIALS AND METHODS: The cytotoxicity and osteogenic effects of P. gingivalis-LPS on BMSCs was evaluated, and then osteoclastic activity of RAW264.7 co-cultured with exosomes was detected. Besides, Affymetrix miRNA array and luciferase reporter assay were used to identify the target exosomal miRNA signal pathway. RESULTS: BMSCs' osteogenic differentiation and proliferation were decreased under 1 and 10 µg/mL P. gingivalis-LPS. Osteoclastic-related genes and proteins levels were promoted by P. gingivalis-LPS-stimulated BMSCs-EXO. Based on the miRNA microarray analysis, exosomal miR-151-3p was lessened in BMExo-LPS group, which facilitated osteoclastic differentiation through miR-151-3p/PAFAH1B1. CONCLUSIONS: Porphyromonas gingivalis-LPS could regulated bone metabolism by inhibiting proliferation and osteogenesis of BMSCs directly. Also, P. gingivalis-LPS-stimulated BMSCs-EXO promoted osteoclastogenesis via activating miR-151-3p/PAFAH1B1 signal pathway.

16.
Biotechnol Bioeng ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38924076

RESUMEN

In this study, a novel array electrospinning collector was devised to generate two distinct regenerated silk fibroin (SF) fibrous membranes: ordered and disordered. Leveraging electrostatic forces during the electrospinning process allowed precise control over the orientation of SF fiber, resulting in the creation of membranes comprising both aligned and randomly arranged fiber layers. This innovative approach resulted in the development of large-area membranes featuring exceptional stability due to their alternating patterned structure, achievable through expansion using the collector, and improving the aligned fiber membrane mechanical properties. The study delved into exploring the potential of these membranes in augmenting wound healing efficiency. Conducting in vitro toxicity assays with adipose tissue-derived mesenchymal stem cells (AD-MSCs) and normal human dermal fibroblasts (NHDFs) confirmed the biocompatibility of the SF membranes. We use dual perspectives on exploring the effects of different conditioned mediums produced by cells and structural cues of materials on NHDFs migration. The nanofibers providing the microenvironment can directly guide NHDFs migration and also affect the AD-MSCs and NHDFs paracrine effects, which can improve the chemotaxis of NHDFs migration. The ordered membrane, in particular, exhibited pronounced effectiveness in guiding directional cell migration. This research underscores the revelation that customizable microenvironments facilitated by SF membranes optimize the paracrine products of mesenchymal stem cells and offer valuable physical cues, presenting novel prospects for enhancing wound healing efficiency.

18.
Am J Cancer Res ; 14(4): 1561-1576, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38726259

RESUMEN

Lung squamous cell carcinoma (LUSC) remains a difficult-to-treat disease with a poor prognosis. While prominin-1 (PROM1/CD-133) is largely investigated in a variety of malignancies, the role of prominin-2 (PROM2), the other member of the prominin family, has not been studied in LUSC. Transcriptomic data derived from matched tumor and adjacent non-tumorous lung tissues of LUSC patients were employed to conduct an in-depth analysis of the genetic and epigenetic regulation of prominin genes within LUSC, utilizing bioinformatic approaches. Furthermore, cellular behavior experiments were executed to discern the biological functions of PROM2. It was observed that PROM2, in contrast to PROM1, exhibited significant upregulation and overexpression at both the mRNA and protein levels in LUSC, and this upregulation was correlated with shortened patient survival. Transcriptomic analysis unveiled DNA methylation as an epigenetic regulatory mechanism associated with PROM2 expression. Notably, two transcription factors, CBFB and NRIP1, were identified as potential regulators of PROM2 expression. Subsequent in vitro investigations demonstrated that knocking down PROM2 led to the inhibition of cancer cell migration and the epithelial-to-mesenchymal transition (EMT). In summary, the pronounced upregulation of PROM2 in LUSC patients was linked to an unfavorable prognosis, possibly attributable to its influence on cancer cell migration and EMT. These findings suggest that PROM2 could serve as a promising diagnostic biomarker and therapeutic target in the management of LUSC. Consequently, further research into the mechanistic aspects and potential therapeutic interventions targeting PROM2 is warranted in the clinical context.

19.
Virus Res ; 345: 199387, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38719025

RESUMEN

Influenza A virus can infect respiratory tracts and may cause severe illness in humans. Proteins encoded by influenza A virus can interact with cellular factors and dysregulate host biological processes to support viral replication and cause pathogenicity. The influenza viral PA protein is not only a subunit of influenza viral polymerase but also a virulence factor involved in pathogenicity during infection. To explore the role of the influenza virus PA protein in regulating host biological processes, we performed immunoprecipitation and LC‒MS/MS to globally identify cellular factors that interact with the PA proteins of the influenza A H1N1, 2009 pandemic H1N1, and H3N2 viruses. The results demonstrated that proteins located in the mitochondrion, proteasome, and nucleus are associated with the PA protein. We further discovered that the PA protein is partly located in mitochondria by immunofluorescence and mitochondrial fractionation and that overexpression of the PA protein reduces mitochondrial respiration. In addition, our results revealed the interaction between PA and the mitochondrial matrix protein PYCR2 and the antiviral role of PYCR2 during influenza A virus replication. Moreover, we found that the PA protein could also trigger autophagy and disrupt mitochondrial homeostasis. Overall, our research revealed the impacts of the influenza A virus PA protein on mitochondrial function and autophagy.


Asunto(s)
Mitocondrias , Proteínas Virales , Replicación Viral , Humanos , Mitocondrias/metabolismo , Mitocondrias/virología , Proteínas Virales/metabolismo , Proteínas Virales/genética , ARN Polimerasa Dependiente del ARN/metabolismo , ARN Polimerasa Dependiente del ARN/genética , Virus de la Influenza A/fisiología , Virus de la Influenza A/genética , Virus de la Influenza A/patogenicidad , Virus de la Influenza A/metabolismo , Interacciones Huésped-Patógeno , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/fisiología , Subtipo H3N2 del Virus de la Influenza A/metabolismo , Autofagia , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/fisiología , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Células HEK293 , Gripe Humana/virología , Gripe Humana/metabolismo , Células A549 , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Espectrometría de Masas en Tándem
20.
Org Lett ; 26(22): 4716-4720, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38802298

RESUMEN

To realize strong donor-acceptor face-to-face stacking for efficient through-space charge transfer-type thermally activated delayed fluorescence, a conceptually new design strategy is proposed to couple flexible bridges with adequate rigidity via built-in intramolecular hydrogen bonds (IHBs). The resulting emitter ACE-CN has a planarized benzyl methyl ether bridge self-anchored by the C-H···O IHB and shows a high photoluminescence quantum efficiency of 93%. The solution- and vacuum-processed devices exhibited high external quantum efficiencies of 11.8% and 24.7%, respectively.

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