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1.
Adv Healthc Mater ; : e2401412, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39268836

RESUMO

Clinically, conventional sutures for repair of short-distance nerve injuries (< 5 mm) may contribute to uncontrolled inflammation and scar formation, thus negatively impacting nerve regeneration. To repair transected peripheral nerves with short distances, a rapid-forming, robust adhesive chitosan hydrogel is prepared by synthesizing maleic and dopamine bi-functionalized fungal-sourced chitosan (DM) and subsequently photopolymerizing DM precursor solution. The hydrogel rapidly polymerized under UV light irradiation (≈2 s) and possessed a strong adhesive strength (273.33 ± 55.07 kPa), facilitating a fast bonding of nerve stump. Especially, its tailored degradation profile over 28 days supported both early gap bridging and subsequent nerve regeneration. Furthermore, deferoxamine (DFO), a pro-angiogenic drug, is loaded into the hydrogel to reach sustainable release, accelerating axonal growth synergistically. A 3 mm long sciatic nerve defects model in rats is used to investigate the efficacy of DM@DFO hydrogel for repairing peripheral nerve defects. After 60 days, the DM@DFO hydrogel significantly outperformed conventional sutures and fibrin glue, improving motor and sensory recovery by reducing inflammation, inhibiting scar formation, and accelerating vascular regeneration within 14 days post-repair. This work highlights the DM@DFO hydrogel as a promising tissue adhesive for effective short-distance peripheral nerve repair.

2.
Chem Biodivers ; : e202401199, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39313870

RESUMO

This study aimed to elucidate the mechanism that total alkaloids in Anisodus tanguticus (AT)(Maxim.) Pascher play anti-inflammatory and analgesic effects. In this paper, the anti-inflammatory effect in the total alkaloids of AT was confirmed via lipopolysaccharide (LPS)-induced inflammation model in RAW 264.7 cells and the main components of AT were immediately analyzed by UPLC/MS. Disease targets were obtained in GeneCards and DisGeNET. Targets of major compounds were searched in ETCM, TCMSP and other databases. The protein-protein interaction (PPI) network was constructed using STRING database, and Cytoscape was used for core targets screening. GO and KEGG enrichment analysis were performed using Daivid database. Sailvina was used for molecular docking. Molecular dynamics simulation analysis was performed using the Amber 20 program. The results showed that the main components in AT were anisodamine, atropine, fabiatrin, scopolamine, scopoletin and scopolin, possibly exerting anti-inflammatory and analgesic effects through pathways such as EGFR tyrosine kinase inhibitor resistance and IL-17 signaling pathway. Fabiatrin and scopolin could be potential drugs with good anti-inflammatory and analgesic effects.

3.
Front Hum Neurosci ; 18: 1445397, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39323957

RESUMO

Introduction: Deaf students have more difficulties with emotion regulation due to their hearing loss. They are suffering higher socio-emotional risk than the hearing person. But there are few studies explored the neural mechanisms of impaired emotion regulation in the deaf college students. Methods: Thirty hearing college students and 27 deaf college students completed the emotion regulation task while recording ERP data and subjective emotion intensity. Results: Behavioral results found that deaf college students had higher emotional experience intensity compared to healthy controls. The ERP results showed the deaf college students had lower LPP amplitudes both using reappraisal and suppression strategies. Moreover, the LPP of expression suppression was associated with the increase of depression scores among deaf college students. Discussion: Deaf college students may have impaired emotion regulation so that they are more accustomed to using expression suppression strategies to regulate their negative emotions which lead to high risk to be depression.

4.
J Am Chem Soc ; 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333048

RESUMO

Lithium (Li) metal batteries hold significant promise in elevating energy density, yet their performance at ultralow temperatures remains constrained by sluggish charge transport kinetics and the formation of unstable interphases. In conventional electrolyte systems, lithium ions are tightly locked in the solvation structure, thereby engendering difficulty in the desolvation process and further exacerbating solvent decomposition. Herein, we propose a new push-pull electrolyte design strategy, utilizing molecular electrostatic potential (ESP) screening to identify 2,2-difluoroethyl trifluoromethanesulfonate (DTF) as an optimal cosolvent. Importantly, DTF exhibits a moderate ESP minimum (-21.0 kcal mol-1) to strike a balance between overly strong and overly weak Li ion affinity, which allows the sulfonyl group to effectively pull Li ions without disrupting the anion-rich solvation structure. Simultaneously, the difluoromethyl group, with a high ESP maximum (37.3 kcal mol-1), pushes solvent molecules via competitive hydrogen bonding. This design reconstructs existing solvation structures and expedites Li ion desolvation. Furthermore, fluorinated DTF demonstrates excellent stability at elevated voltage and facilitates the formation of robust inorganic-rich interphases. Impressively, rapid charge transfer kinetics can be achieved employing designed electrolyte, and the LiNi0.8Mn0.1Co0.1O2 (NMC811)||Li cells demonstrate excellent charge-discharge cycling stability with a high capacity exceeding 153 mAh g-1 even at -40 °C, retaining over 93% of initial capacity after 100 cycles under a 4.8 V charging cutoff. This work provides insights into the design of low-temperature electrolytes with a wide electrochemical window, advancing the development of batteries for extreme conditions.

5.
PLoS Biol ; 22(9): e3002653, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39292711

RESUMO

The modular structure of functional connectomes in the human brain undergoes substantial reorganization during development. However, previous studies have implicitly assumed that each region participates in one single module, ignoring the potential spatial overlap between modules. How the overlapping functional modules develop and whether this development is related to gray and white matter features remain unknown. Using longitudinal multimodal structural, functional, and diffusion MRI data from 305 children (aged 6 to 14 years), we investigated the maturation of overlapping modules of functional networks and further revealed their structural associations. An edge-centric network model was used to identify the overlapping modules, and the nodal overlap in module affiliations was quantified using the entropy measure. We showed a regionally heterogeneous spatial topography of the overlapping extent of brain nodes in module affiliations in children, with higher entropy (i.e., more module involvement) in the ventral attention, somatomotor, and subcortical regions and lower entropy (i.e., less module involvement) in the visual and default-mode regions. The overlapping modules developed in a linear, spatially dissociable manner, with decreased entropy (i.e., decreased module involvement) in the dorsomedial prefrontal cortex, ventral prefrontal cortex, and putamen and increased entropy (i.e., increased module involvement) in the parietal lobules and lateral prefrontal cortex. The overlapping modular patterns captured individual brain maturity as characterized by chronological age and were predicted by integrating gray matter morphology and white matter microstructural properties. Our findings highlight the maturation of overlapping functional modules and their structural substrates, thereby advancing our understanding of the principles of connectome development.


Assuntos
Encéfalo , Conectoma , Rede Nervosa , Humanos , Criança , Conectoma/métodos , Adolescente , Encéfalo/crescimento & desenvolvimento , Encéfalo/diagnóstico por imagem , Encéfalo/anatomia & histologia , Masculino , Feminino , Rede Nervosa/crescimento & desenvolvimento , Rede Nervosa/anatomia & histologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Substância Branca/crescimento & desenvolvimento , Substância Branca/diagnóstico por imagem , Substância Branca/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Substância Cinzenta/crescimento & desenvolvimento , Substância Cinzenta/anatomia & histologia , Substância Cinzenta/diagnóstico por imagem
6.
IEEE Trans Cybern ; PP2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39231065

RESUMO

This article considers an observer-based optimal backstepping security control for nonlinear systems using reinforcement learning (RL) strategy. The main challenge faced is the design of optimal contoller under the deception attacks. Therefore, this article introduces an improved security RL algorithm based on neural network technology under the design framework of critic-actor to resist attacks and optimize the entire system. Second, compared with some existing results, how to relax the general assumption about deception attack is also a difficult research topic. In this article, an unusual observer that uses the attacked system output is designed to estimate the real unavailable states caused by deception attacks, so that the impact of deception attacks is eliminated and the output feedback control is also achieved. By selecting the virtual controllers and the real controller as corresponding optimized controllers within the framework of the RL algorithm, the control strategy can ensure that all signals in the closed-loop system are semi-globally ultimately bounded. Finally, two simulation experiments will be run to demonstrate the effectiveness of the strategy.

7.
Cell Mol Life Sci ; 81(1): 387, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39249529

RESUMO

BACKGROUND: Dysregulated lipid oxidation occurs in several pathological processes characterized by cell proliferation and migration. Nonetheless, the molecular mechanism of lipid oxidation is not well appreciated in liver fibrosis, which is accompanied by enhanced fibroblast proliferation and migration. METHODS: We investigated the causes and consequences of lipid oxidation in liver fibrosis using cultured cells, animal models, and clinical samples. RESULTS: Increased ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP1) expression caused increased lipid oxidation, resulting in the proliferation and migration of hepatic stellate cells (HSCs) that lead to liver fibrosis, whereas fibroblast-specific ENPP1 knockout reversing these results. Elevated ENPP1 and N6-methyladenosine (m6A) levels were associated with high expression of Wilms tumor 1 associated protein (WTAP). Mechanistically, WTAP-mediated m6A methylation of the 3'UTR of ENPP1 mRNA and induces its translation dependent of YTH domain family proteins 1 (YTHDF1). Additionally, ENPP1 could interact with hypoxia inducible lipid droplet associated (HILPDA) directly; overexpression of ENPP1 further recruits HILPDA-mediated lipid oxidation, thereby promotes HSCs proliferation and migration, while inhibition of ENPP1 expression produced the opposite effect. Clinically, increased expression of WTAP, YTHDF1, ENPP1, and HILPDA, and increased m6A mRNA content, enhanced lipid oxidation, and increased collagen deposition in human liver fibrosis tissues. CONCLUSIONS: We describe a novel mechanism in which WTAP catalyzes m6A methylation of ENPP1 in a YTHDF1-dependent manner to enhance lipid oxidation, promoting HSCs proliferation and migration and liver fibrosis.


Assuntos
Adenosina , Proliferação de Células , Metabolismo dos Lipídeos , Cirrose Hepática , Oxirredução , Diester Fosfórico Hidrolases , Pirofosfatases , RNA Mensageiro , Pirofosfatases/metabolismo , Pirofosfatases/genética , Humanos , Diester Fosfórico Hidrolases/metabolismo , Diester Fosfórico Hidrolases/genética , Animais , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Cirrose Hepática/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proliferação de Células/genética , Metabolismo dos Lipídeos/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Movimento Celular/genética , Camundongos Endogâmicos C57BL , Masculino , Epigênese Genética , Fibroblastos/metabolismo , Fibroblastos/patologia , Metilação , Fatores de Processamento de RNA , Proteínas de Ciclo Celular
8.
Zookeys ; 1210: 197-206, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39220724

RESUMO

A new species Serangiumxinpingensis Huang & Wang, sp. nov. is described from Yunnan Province, China, as a newly discovered predator on Bemisiatabaci Gennadius (Hemiptera, Sternorrhyncha, Aleyrodidae). The new species is a valuable addition to the 14 species of this genus in China known before. A diagnosis, detailed description, including the structure of its immature stages, illustrations, and the distribution of the new species are provided.

9.
Autism Res ; 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39243179

RESUMO

Sex heterogeneity has been frequently reported in autism spectrum disorders (ASD) and has been linked to static differences in brain function. However, given the complexity of ASD and diagnosis-by-sex interactions, dynamic characteristics of brain activity and functional connectivity may provide important information for distinguishing ASD phenotypes between females and males. The aim of this study was to explore sex heterogeneity of functional networks in the ASD brain from a dynamic perspective. Resting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange database were analyzed in 128 ASD subjects (64 males/64 females) and 128 typically developing control (TC) subjects (64 males/64 females). A sliding-window approach was adopted for the estimation of dynamic amplitude of low-frequency fluctuation (dALFF) and dynamic functional connectivity (dFC) to characterize time-varying brain activity and functional connectivity respectively. We then examined the sex-related changes in ASD using two-way analysis of variance. Significant diagnosis-by-sex interaction effects were identified in the left anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) and left precuneus in the dALFF analysis. Furthermore, there were significant diagnosis-by-sex interaction effects of dFC variance between the left ACC/mPFC and right ACC, left postcentral gyrus, left precuneus, right middle temporal gyrus and left inferior frontal gyrus, triangular part. These findings reveal the sex heterogeneity in brain activity and functional connectivity in ASD from a dynamic perspective, and provide new evidence for further exploring sex heterogeneity in ASD.

10.
Oncol Lett ; 28(6): 553, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39345721

RESUMO

[This retracts the article DOI: 10.3892/ol.2017.6492.].

11.
Int J Biol Macromol ; 279(Pt 1): 135029, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39197618

RESUMO

Conductive hydrogels with excellent mechanical properties, a broad detection range, and stability in complex environments have remained a significant challenge for the development of flexible sensors. In this study, a straightforward freeze-thaw cycles strategy was developed to fabricate a polyvinyl alcohol (PVA)/carrageenan (CA)/calcium chloride (CaCl2)/MXene-based double network organohydrogel (PCCME) for highly flexible and responsive strain detection across a broad temperature spectrum. The PCCME organohydrogel features multiple interactive forces including hydrogen bonding, ionic interactions, and microphase crystallization, which contribute to the organohydrogel's exceptional mechanical and electrical performance. The PCCME organohydrogel exhibited excellent performance in a load-unload test repeated 100 times after being maintained at room temperature for 7 days, with a minimal mechanical decay of only 2.6%. Furthermore, the repaired PCCME organohydrogel retained its robust stability after storage at low temperatures followed by placement at room temperature. The organohydrogel sensor not only detects various movement amplitudes of the human body but also recognizes arrays of pressure signals and converts these into digital images, highlighting its significant potential for applications in rehabilitation monitoring, pressure sensing, and human-computer interaction.

12.
Food Chem ; 461: 140837, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39151350

RESUMO

Lycium ruthenicum Murr. is mainly distributed in the northwest region of China and its berries are rich in anthocyanin. This study evaluated the hypoglycaemic activity of the anthocyanin-enriched fraction (AEF) of L. ruthenicum Murr. on α-glucosidase in vivo and in vitro. Overall, 10 anthocyanins were identified via UPLC-Triple-TOF-MS/MS. The AEF exhibited strong inhibitory activity against α-glucosidase, with an IC50 value of 4.468 mg/mL. It behaved as a reversible, mixed-type inhibitor. Molecular docking and dynamic results indicated that the compounds in AEF interacted with enzymes primarily through van der Waals and hydrogen bond and the complex system was stable. The postprandial blood glucose and area under the curve of diabetic mice was significantly decreased by AEF in the carbohydrate tolerance experiments. The results indicate that the AEF from L. ruthenicum Murr. berries could be as a promising food supplement for managing blood sugar levels in patients with diabetes mellitus.


Assuntos
Antocianinas , Frutas , Hipoglicemiantes , Lycium , Extratos Vegetais , Espectrometria de Massas em Tandem , Lycium/química , Frutas/química , Animais , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Antocianinas/química , Antocianinas/farmacologia , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Cromatografia Líquida de Alta Pressão , Masculino , Humanos , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo , Glicemia/metabolismo , Simulação de Acoplamento Molecular , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia
13.
J Ethnopharmacol ; 335: 118657, 2024 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-39127115

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sea buckthorn (Hippophae rhamnoides L.) is a traditional Chinese medicinal and possesses a rich medical history in terms of treating gastric disorders, sputum and cough and liver injuries in oriental medicinal system. By reason of the complicated chemical constituents, the material basis and potential pharmacological mechanism of sea buckthorn acting on Non-alcoholic fatty liver disease (NAFLD) has not been clearly elucidated. AIM OF THE STUDY: To explore the pharmacological efficacy and underlying mechanism of sea buckthorn triterpenoid acid enrichment (STE) in the treatment of NAFLD. MATERIALS AND METHODS: The approaches of Network pharmacology and experiment validation in vitro and in vivo were applied in this study. Firstly, targets of triterpenoid acid compounds and NAFLD were collected from databases. The crucial targets were screened by the construction of protein-protein interaction (PPI) network. Furthermore, the potential signaling pathways and targets affected by STE was predicted by GO together with KEGG enrichment analysis. Finally, the experiment validation was carried out through high-fat feeding NAFLD mice and lipid accumulation HepG2 cell model. Lipids and liver related biochemical indicators were determined, Oil Red O and H&E staining were employed to observe fat accumulation. In addition, the expression levels of proteins of key target and signal pathway anticipated in network pharmacology were detected to elaborated its action mechanism. RESULTS: A total of 180 intersecting potential targets for enhancing NAFLD with STE were eventually identified. 6 key targets including AKT1, TNF, IL6, INS, JUN, STAT3 and TP53 were further identified and the AMPK-SREBP1 pathway was enriched. Animal experiment result showed that STE treatment could significantly reduce the levels of TG, TC, LDL-C, ALT and AST, increase the levels of HDL-C in serum, and improve lipid accumulation of epididymal fat and liver. The results of the lipid accumulation cell model indicated that STE and key compound oleanolic acid could diminish intracellular lipid levels of TG, TC, LDL-C and number of lipid droplets. Western blot results showed that the above beneficial effects could be achieved by regulating the expression of p-AMPK/AMPK, SREBP1, FAS, ACC, SCD protein. CONCLUSION: This study confirmed the effect of STE on improving NAFLD and the potential action mechanism was involved in the regulation of the AMPK-SREBP1 pathway.


Assuntos
Hippophae , Farmacologia em Rede , Hepatopatia Gordurosa não Alcoólica , Triterpenos , Hippophae/química , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Triterpenos/farmacologia , Humanos , Masculino , Células Hep G2 , Camundongos , Camundongos Endogâmicos C57BL , Mapas de Interação de Proteínas , Dieta Hiperlipídica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos
14.
Brain Sci ; 14(8)2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39199481

RESUMO

To better understand the individual differences in fairness, we used event-related potentials (ERPs) to explore the fairness characteristics of deaf college students through the ultimatum game task. Behaviorally, the significant main effect of the proposal type was found, which meant both deaf and hearing college students showed a lower acceptance rate for the more unfair proposal. Interestingly, we found a significant interaction between group and proposal type in the early stage (N1). Moreover, in the deaf college group, N1 (induced by moderately and very unfair proposals) was significantly larger than that of fair proposals. However, we found that deaf college students had smaller amplitudes on P2 and P3 than hearing college students. These results suggested that deaf college students might pursue more equity strongly so they are more sensitive to unfair information in the early stage. In a word, we should provide more fair allocations for deaf college students in our harmonious society.

15.
Cancer Cell Int ; 24(1): 296, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39180066

RESUMO

BACKGROUND: Vascular endothelial growth factor (VEGF) is an important proangiogenic factor and has been considered as a key target of antiangiogenetic therapy in oral squamous cell carcinoma (OSCC). However, clinical application of bevacizumab, a specific VEGF antibody, didn't improve the survival rate of OSCC patients. One possible explanation is that VEGF gene expresses diverse isoforms, which associate with extracellular vesicles (EVs), and EVs potentially contribute to VEGF resistance to bevacizumab. However, clear solution is lacking in addressing this issue. METHODS: Expression of VEGF isoforms in OSCC cells was confirmed by reverse transcription and polymerase chain reaction (RT-PCR) and western blot. EVs isolated from OSCC cell's conditioned medium (CM) were characterized by western blot, transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Flow cytometry, immunogold labeling and western blot were applied to study the VEGF on EVs. Tube formation assay and Matrigel plug angiogenesis assay were used for analyzing the angiogenesis capacity of EV-VEGF. RESULTS: The most popular isoforms expressed by VEGF gene are VEGF121, VEGF165 and VEGF189. In this study, we demonstrated that all three isoforms of mRNA could be detected at varying levels in OSCC cells, while only VEGF165 and VEGF189 proteins were found. CM derived from OSCC cells, both soluble and non-soluble forms of VEGF could be detected. We further confirmed the presence of VGEF189 bound to EVs as a non-soluble form. EV-bound VEGF189 presented angiogenic activity, which could not be neutralized by bevacizumab. It was found that VEGF189 bound to EVs by heparan sulfate proteoglycans (HSPG). In addition, the angiogenic effect of EV-VEGF could be reversed by surfen, a kind of HSPG antagonist both in vitro and in vivo. CONCLUSION: Antagonists targeting HSPG might potentially overcome the resistance of EV-VEGF to bevacizumab and serve as an alternative for anti-VEGF therapy in OSCC.

16.
Food Chem X ; 23: 101626, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39108629

RESUMO

This study aimed to optimize subcritical water extraction process, characterize chemical composition and investigate the biological activities of Nitraria sibirica Pall. (NSP) anthocyanin. Overall, the optimization was achieved under following conditions: extraction temperature 140 °C, extraction time 45 min and flow rate 7 mL/min with the extraction yield of 1.075 mg/g. 3 cyanidin, 3 petunidin, 1 delphinidin and 1 pelargonidin compounds were identified in the anthocyanic extract from NSP via UPLC-Triple-TOF-MS/MS. NSP anthocyanin exhibited better DPPH free-radical scavenging activity than ascorbic acid. It displayed superior α-glucosidase inhibition activity, which was ∼14 times higher than that of acarbose. Moreover, enzyme kinetics results indicated that NSP anthocyanin behaved as a reversible, mixed-type inhibitor. Molecular docking and molecular dynamics simulation results revealed that NSP anthocyanin interacted with α-glucosidase mainly via van der Waals forces, hydrogen bond and possessed fairly stable configuration. Therefore, NSP anthocyanin is a promising α-glucosidase inhibitor for diabetes mellitus.

17.
Front Pediatr ; 12: 1417649, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39100650

RESUMO

Background: Dubin-Johnson Syndrome (DJS) is a rare autosomal recessive genetic disorder, with most cases presenting in adolescence, but rare in newborns. Objective: To investigate the clinical characteristics and treatment outcomes of DJS in a newborn. Methods: We present the clinical features of a newborn diagnosed with DJS through molecular genetic testing. Results: The patient was a male newborn who developed jaundice and scleral icterus on the 6th day of life. Both direct and indirect bilirubin levels were elevated. After treatment with phototherapy, indirect bilirubin levels decreased, but direct bilirubin remained unchanged, and the stool color gradually lightened. At 56 days of age, the patient underwent laparoscopic cholecystostomy, which revealed viscous bile plugs in the bile ducts. Following the surgery, the patient received oral ursodeoxycholic acid, compound glycyrrhizin, and methylprednisolone. Follow-up until one year post-surgery showed a gradual reduction in direct bilirubin levels to the normal range. Molecular genetic testing revealed three heterozygous mutations in the ABCC2 gene on chromosome 10, with one pathogenic variant inherited from the father and two from the mother, confirming the diagnosis of DJS. Conclusion: DJS is a benign condition with a favorable prognosis. In newborns, it should be differentiated from other causes of cholestasis, and compared to cholestasis, jaundice in newborns with DJS responds more slowly to treatment.

18.
J Transl Med ; 22(1): 804, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39210391

RESUMO

BACKGROUND: The metastasis of cancer cells is influenced by both their intrinsic characteristics and the tumor microenvironment (TME). However, the molecular mechanisms underlying pre-nodal metastases of breast cancer remain unclear. METHODS: We integrated a total of 216,963 cells from 54 samples across 6 single-cell datasets to profile the cellular landscape differences between primary tumors and pre-nodal metastases. RESULTS: We revealed three distinct metastatic epithelial cell subtypes (Epi1, Epi2 and Epi3), which exhibited different metastatic mechanisms. Specifically, the marker gene KCNK15 of the Epi1 subtype exhibited increased gene expression along the cell differentiation trajectory and was specifically regulated by the transcription factor ASCL1. In the Epi3 subtype, we highlighted NR2F1 as a regulator targeting the marker gene MUCL1. Additionally, we found that the Epi2 and Epi3 subtypes shared some regulons, such as ZEB1 and NR2C1. Similarly, we identified specific subtypes of stromal and immune cells in the TME, and discovered that vascular cancer-associated fibroblasts might promote capillary formation through CXCL9+ macrophages in pre-nodal metastases. All three subtypes of metastatic epithelial cells were associated with poor prognosis. CONCLUSIONS: In summary, this study dissects the intratumoral heterogeneity and remodeling of the TME in pre-nodal metastases of breast cancer, providing novel insights into the mechanisms underlying breast cancer metastasis.


Assuntos
Neoplasias da Mama , Regulação Neoplásica da Expressão Gênica , Heterogeneidade Genética , Metástase Neoplásica , Análise de Célula Única , Microambiente Tumoral , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Feminino , Células Epiteliais/patologia , Células Epiteliais/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia
19.
Biomed Chromatogr ; : e5989, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39171645

RESUMO

Epilepsy (EP) is one of the most common neurological diseases in the world. Anemarrhena asphodeloides Bunge. (AA), as a typical heat-cleaning medicine, has been proven to possess the antiepileptic effect in clinical and experimental studies. Anemarrhena asphodeloides steroidal saponins (AAS) are main components. However, the therapeutic effects and underlying mechanisms of AAS against EP are not been fully elucidated. In this study, 63 steroidal saponins were discovered in AAS by UPLC-Q-TOF/MS analysis. Pharmacological and behavioral analysis demonstrated that AAS could significantly lower the Racine classification and reduce the frequency of generalized spike rhythm the rate of tetanic seizures in kainic acid-induced epileptic rats. Hematoxylin and eosin and Nissl staining-indicated AAS could significantly improve hippocampal injury and neuron loss in epileptic rats. TMT proteomic analysis discovered 26 different expressed proteins (DEPs), which were identified as the rescue proteins. After bioinformatic analysis, Heat Shock Protein 90 Alpha Family Class B Member 1 (Hsp90ab1) and Tyrosine 3-Monooxygenase (Ywhab) were screened as key DEPs and verified by western blotting. AAS could significantly inhibited the up-regulation of Hsp90ab1 and Ywhab in EP rats; these two proteins might be the key targets of AAS in treating EP.

20.
Cell Signal ; 122: 111302, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39025344

RESUMO

Liver fibrosis is a pathological process caused by a variety of chronic liver diseases. Currently, therapeutic options for liver fibrosis are very limited, highlighting the urgent need to explore new treatment approaches. Epigenetic modifications and epitranscriptomic modifications, as reversible regulatory mechanisms, are involved in the development of liver fibrosis. In recent years, researches in epitranscriptomics and epigenetics have opened new perspectives for understanding the pathogenesis of liver fibrosis. Exploring the epigenetic mechanisms of liver fibrosis may provide valuable insights into the development of new therapies for chronic liver diseases. This review primarily focus on the regulatory mechanisms of N6-methyladenosine (m6A) modification, non-coding RNA, and DNA methylation in organ fibrosis. It discusses the interactions between m6A modification and DNA methylation, as well as between m6A modification and non-coding RNA, providing a reference for understanding the interplay between epitranscriptomics and epigenetics.


Assuntos
Adenosina , Metilação de DNA , Epigênese Genética , Cirrose Hepática , RNA não Traduzido , Humanos , Cirrose Hepática/genética , Cirrose Hepática/patologia , Cirrose Hepática/metabolismo , RNA não Traduzido/metabolismo , RNA não Traduzido/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Transcriptoma
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