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1.
Neuroimage ; 297: 120763, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39084280

RESUMO

Human brain gray matter (GM) has usually been clustered into multiple functional networks. The white matter (WM) fiber bundles are known to interconnect these networks simultaneously, engaging in numerous cognitive functions. However, the exact interconnections between GM and WM are still unclear, whether functional signals in WM rewires GM community organization remains to be explored. In this study, we divided brain functional connections into three types by using edge-centric method, including intra-GM, intra-WM and GM-WM connections, and calculated the edge community evaluation indexes for quantifying GM community engagement. The results showed that the involvement of WM significantly enhanced community entropy in the heteromodal system, while the sensory-attention system remained barely changed. In addition, delta community entropy showed a significant correlation with clinical cognitive scale. Our results suggested that WM rewired GM community organization, enhancing the community engagement of brain regions in the heteromodal system. This involvement was observed to be disrupted in disease groups. Our study revealed that considering the functional signals of GM and WM simultaneously could better understand the brain's functional organization.


Assuntos
Substância Cinzenta , Imageamento por Ressonância Magnética , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/fisiologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/anatomia & histologia , Substância Cinzenta/fisiologia , Masculino , Feminino , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Idoso
2.
Small ; : e2401717, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39286887

RESUMO

Skull morphogenesis is a complex, dynamic process involving two different germ layers and progressing to the coordinated, directional growth of individual bones. The mechanisms underlying directional growth toward the apex are not completely understood. Here, a microfluidic chip-based approach is utilized to test whether calvarial osteoblast progenitors undergo haptotaxis on a gradient of Fibronectin1 (FN1) via lamellipodia. Mimicking the embryonic cranial mesenchyme's FN1 pattern, FN1 gradients is established in the chip using computer modeling and fluorescent labeling. Primary mouse calvarial osteoblast progenitors are plated in the chip along an array of segmented gradients of adsorbed FN1. The study performs single-cell tracking and measures protrusive activity. Haptotaxis is observed at an intermediate FN1 concentration, with an average directional migration index (yFMI) of 0.07, showing a significant increase compared to the control average yFMI of -0.01. A significant increase in protrusive activity is observed during haptotaxis. Haptotaxis is an Arp2/3-dependent, lamellipodia-mediated process. Calvarial osteoblast progenitors treated with the Arp2/3 (Actin Related Protein 2/3 complex) inhibitor CK666 show significantly diminished haptotaxis, with an average yFMI of 0.01. Together, these results demonstrate haptotaxis on an FN1 gradient as a new mechanism in the apical expansion of calvarial osteoblast progenitors during development and shed light on the etiology of calvarial defects.

3.
Small ; 20(12): e2307104, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37939306

RESUMO

The treatment of chronic wounds still presents great challenges due to being infected by biofilms and the damaged healing process. The current treatments do not address the needs of chronic wounds. In this study, a highly effective dressing (Dox-DFO@MN Hy) for the treatment of chronic wounds is described. This dressing combines the advantages of microneedles (MNs) and hydrogels in the treatment of chronic wounds. MNs is employed to debride the biofilms and break down the wound barrier, providing rapid access to therapeutic drugs from hydrogel backing layer. Importantly, to kill the pathogenic bacteria in the biofilms specifically, Doxycycline hydrochloride (Dox) is wrapped into the polycaprolactone (PCL) microspheres that have lipase-responsive properties and loaded into the tips of MNs. At the same time, hydrogel backing layer is used to seal the wound and accelerate wound healing. Benefiting from the combination of two advantages of MNs and hydrogel, the dressing significantly reduces the bacteria in the biofilms and effectively promotes angiogenesis and cell migration in vitro. Overall, Dox-DFO@MN Hy can effectively treat chronic wounds infected with biofilms, providing a new idea for the treatment of chronic wounds.


Assuntos
Bandagens , Hidrogéis , Bactérias , Biofilmes , Movimento Celular , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
4.
Bioorg Chem ; 143: 107018, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38071874

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a fatal, chronic and progressive lung disease that threaten public health like many cancers. In this study, targeting the significant driving factor, inflammatory response, of the IPF, several conjugates of pirfenidone (PFD) with non-steroidal anti-inflammatory drugs (NSAIDs), along with their derivatives, were designed and synthesized to enhance the anti-IPF potency of PFD. Among these compounds, the (S)-ibuprofen-PFD conjugate 5b exhibited the most potent anti-proliferation activity against NIH3T3 cells, demonstrating up to a 343-fold improvement compared to PFD (IC50 = 0.04 mM vs IC50 = 13.72 mM). Notably, 5b exhibited superior activity in inhibiting the migration of macrophages induced by TGF-ß compared to PFD. Additionally, 5b demonstrated significant suppression of TGF-ß-induced migration of NIH3T3 cells and induction of apoptosis in NIH3T3 cells. Mechanistic studies revealed that 5b reduced the expression of collagen I and α-SMA by inhibiting the TGF-ß/SMAD3 pathway. In a bleomycin-induced pulmonary fibrosis model, treatment with 5b (40 mg/kg/day, orally) exhibited a more pronounced effect on reducing the degree of histopathological changes in lung tissue and alleviating collagen deposition compared to PFD (100 mg/kg/day, orally). Moreover, 5b could block the expression of collagen I, α-SMA, fibronectin, and pro-inflammatory factors (IL-6, IFN-γ, and TNF-α) compared to PFD, while demonstrating low toxicity in vivo. These preliminary results indicated that the hybridization of PFD with NSAIDs represented an effective modification approach to improve the anti-IPF potency of PFD. Consequently, 5b emerged as a promising candidate for the further development of new anti-IPF agents.


Assuntos
Fibrose Pulmonar Idiopática , Animais , Camundongos , Humanos , Células NIH 3T3 , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Piridonas/farmacologia , Piridonas/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Colágeno/metabolismo , Colágeno/uso terapêutico , Colágeno Tipo I/metabolismo , Fator de Crescimento Transformador beta/metabolismo
5.
Angew Chem Int Ed Engl ; : e202412896, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39363695

RESUMO

The development of high-voltage lithium metal batteries (LMBs) encounters significant challenges due to aggressive electrode chemistry. Recently, locally concentrated ionic liquid electrolytes (LCILEs) have garnered attention for their exceptional stability with both Li anodes and high-voltage cathodes. However, there remains a limited understanding of how diluents in LCILEs affect the thermodynamic stability of the solvation structure and transportation dynamics of Li+ ions. Herein, we propose a wide-temperature LCILEs with 1,3-dichloropropane (DCP13) diluent to construct a non-equilibrium solvation structure under external electric field, wherein the DCP13 diluent enters the Li+ ion solvation sheath to enhance Li+ ion transport and suppress oxidative side reactions at high-nickel cathode (LiNi0.9Co0.05Mn0.05O2, NCM90).Consequently, a Li/NCM90 cell utilizing this LCILE achieves a high capacity retention of 94% after 240 cycles at 4.3 V, also operates stably at high cut-off voltages from 4.4 to 4.6 V and over a wide temperature range from -20 to 60 °C. Additionally, an Ah-level pouch cell with this LCILE simultaneously achieves high-energy-density and stable cycling, manifesting the practical feasibility. This work redefines the role of diluents in LCILEs, providing inspiration for electrolyte design in developing high-energy-density batteries.

6.
Environ Res ; 232: 116339, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37290628

RESUMO

Chlortetracycline hydrochloride (CTC) is one of the prevailing antibiotic pollutants that harm both environmental ecosystem and human health. Herein, Zr-based metal-organic gels (Zr-MOGs) with lower-coordinated active sites and hierarchically porous structures are fabricated via a facile straightforward room-temperature strategy for CTC treatment. More importantly, we incorporated the powder Zr-MOGs into low-cost sodium alginate (SA) matrix to achieve shaped Zr-based metal-organic gel/SA beads for enhancing the adsorption ability and ameliorating the recyclability. The Langmuir maximum adsorption capacities of Zr-MOGs and Zr-MOG/SA beads could reach 143.9 mg/g and 246.9 mg/g, respectively. What's more, in the manual syringe unit and continuous bead column experiments, Zr-MOG/SA beads could achieve an eluted CTC removal ratio as high as 96.3% and 95.5% in the river water sample, respectively. On top of that, the adsorption mechanisms were put forward as a combination of pore filling, electrostatic interaction, hydrophilic-lipophilic balance, coordination, π-π interaction as well as hydrogen bonding interaction. This study outlines a workable strategy for the facile preparation of candidate adsorbents for wastewater treatment.


Assuntos
Clortetraciclina , Poluentes Químicos da Água , Humanos , Clortetraciclina/química , Água , Temperatura , Alginatos/química , Adsorção , Ecossistema , Metais , Géis/química , Poluentes Químicos da Água/análise , Cinética , Concentração de Íons de Hidrogênio
7.
Phys Chem Chem Phys ; 24(38): 23779-23789, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36156612

RESUMO

Filaments driven by bound motor proteins and chains of self-propelled colloidal particles are a typical example of active polymers (APs). Due to deformability, APs exhibit very rich dynamic behaviors and collective assembling structures. Here, we are concerned with a basic question: how APs behave near a single obstacle? We find that, in the presence of a big single obstacle, the assembly of APs becomes a two-state system, i.e. APs either gather nearly completely together into a giant jammed aggregate (GJA) on the surface of the obstacle or distribute freely in space. No partial aggregation is observed. Such a complete aggregation/collection is unexpected since it happens on a smooth convex surface instead of, e.g., a concave wedge. We find that the formation of a GJA experiences a process of nucleation and the curves of the transition between the GJA and the non-aggregate state form hysteresis-like loops. Statistical analysis of massive data on the growing time, chirality and angular velocity of both the GJAs and the corresponding nuclei shows the strong random nature of the phenomenon. Our results provide new insights into the behavior of APs in contact with porous media and also a reference for the design and application of polymeric active materials.


Assuntos
Polímeros
8.
Neurochem Res ; 46(3): 675-685, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33471295

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disorder disease, disturbing people's normal life. Syringin was mentioned to antagonize Amyloid-ß (Aß)-induced neurotoxicity. However, the action mechanism is still not fully elucidated. This study aimed to explore a molecular mechanism of syringin in defending Aß-induced neurotoxicity. SK-N-SH and SK-N-BE cells were treated with amyloid ß-protein fragment 25-35 (Aß25-35) to induce cell neurotoxicity. The injury effects were distinguished by assessing cell viability and cell apoptosis using cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The expression of Cleaved-caspase3 (Cleaved-casp3), B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and BH3 interacting domain death agonist (BID) at the protein level was determined by western blot. The expression of miR-124-3p and BID was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-124-3p and BID was predicted by the online database starBase and confirmed by dual-luciferase reporter assay plus RNA pull-down assay. Aß25-35 treatment inhibited cell viability and induced cell apoptosis, while the addition of syringin recovered cell viability and suppressed cell apoptosis. MiR-124-3p was significantly downregulated in Aß25-35-treated SK-N-SH and SK-N-BE cells, and BID was upregulated. Nevertheless, the addition of syringin reversed their expression. BID was a target of miR-124-3p, and its downregulation partly prevented Aß25-35-induced injuries. Syringin protected against Aß25-35-induced neurotoxicity by enhancing miR-124-3p expression and weakening BID expression, and syringin strengthened the expression of miR-124-3p to diminish BID level. Syringin ameliorated Aß25-35-induced neurotoxicity in SK-N-SH and SK-N-BE cells by regulating miR-124-3p/BID pathway, which could be a novel theoretical basis for syringin to treat AD.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3/metabolismo , Glucosídeos/farmacologia , MicroRNAs/metabolismo , Fragmentos de Peptídeos/toxicidade , Fenilpropionatos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Humanos , Regulação para Cima
9.
Neurochem Res ; 45(11): 2679-2690, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32857295

RESUMO

Neuroblastoma (NB) is a heterogeneous tumor that is common in infants and young children. Long non-coding RNA X-inactive specific transcript (XIST) is implicated in NB advancement. Nevertheless, the role and regulatory mechanism by which XIST in NB are not fully elucidated. Expression levels of XIST, microRNA-375-5p (miR-375), and L1 cell adhesion molecular (L1CAM) were examined through quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle progression, proliferation, and colony formation of NB cells were determined with flow cytometry, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), or cell colony formation assays. Cell apoptotic rate was detected with flow cytometry assay. The relationship between XIST or L1CAM and miR-375 was verified via dual-luciferase reporter assay. The level of L1CAM protein was examined through western blotting. The role of XIST in vivo was confirmed through xenograft assay. XIST and L1CAM were upregulated while miR-375 was downregulated in NB tissues and cells. XIST depletion repressed tumor growth in vivo and elevated radiosensitivity, arrested cell cycle progression, and impeded proliferation of NB cells in vitro. Mechanistically, XIST modulated L1CAM expression through competitively binding to miR-375. Furthermore, miR-375 inhibitor recovered XIST inhibition-mediated effects on the radiosensitivity and malignant behaviors of NB cells. Also, L1CAM overexpression reversed the effects of miR-375 enhancement on the cell cycle progression, proliferation, and radiosensitivity of NB cells. XIST downregulation repressed tumor growth and boosted radiosensitivity of NB via modulating the miR-375/L1CAM axis, indicating that XIST was a promising target for NB treatment.


Assuntos
Proliferação de Células/fisiologia , MicroRNAs/metabolismo , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Neuroblastoma/fisiopatologia , RNA Longo não Codificante/genética , Tolerância a Radiação/fisiologia , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , RNA Longo não Codificante/metabolismo , Regulação para Cima
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(3): 174-177, 2018 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29530114

RESUMO

OBJECTIVE: To study the risk factors for elevated serum total bile acid (TBA) in preterm infants. METHODS: A retrospective analysis was performed for the clinical data of 216 preterm infants who were admitted to the neonatal intensive care unit. According to the presence or absence of elevated TBA (TBA >24.8 µmol/L), the preterm infants were divided into elevated TBA group with 53 infants and non-elevated TBA group with 163 infants. A univariate analysis and an unconditional multivariate logistic regression analysis were used to investigate the risk factors for elevated TBA. RESULTS: The univariate analysis showed that there were significant differences between the elevated TBA group and the non-elevated TBA group in gestational age at birth, birth weight, proportion of small-for-gestational-age infants, proportion of infants undergoing ventilator-assisted ventilation, fasting time, parenteral nutrition time, and incidence of neonatal respiratory failure and sepsis (P<0.05). The unconditional multivariate logistic regression analysis showed that low birth weight (OR=3.84, 95%CI: 1.53-9.64) and neonatal sepsis (OR=2.56, 95%CI: 1.01-6.47) were independent risk factors for elevated TBA in preterm infants. CONCLUSIONS: Low birth weight and neonatal sepsis may lead to elevated TBA in preterm infants.


Assuntos
Ácidos e Sais Biliares/sangue , Recém-Nascido Prematuro/sangue , Feminino , Humanos , Recém-Nascido de Baixo Peso/sangue , Recém-Nascido , Modelos Logísticos , Masculino , Estudos Retrospectivos , Fatores de Risco , Sepse/sangue
12.
Zhonghua Nan Ke Xue ; 22(4): 325-9, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30088409

RESUMO

Objective: To compare the incidences of Y chromosome microdeletion between patients with azoospermia or severe oligozoospermia with varicocele( VC) and those without VC and investigate the etiopathogenisis of their infertility. Methods: We included 137 VC patients in group A(70 with azoospermia as group A1 and 67 with severe oligozoospermia as group A2),135 non-VC patients in group B(69 with azoospermia as group B1 and 66 with severe oligozoospermia as group B2),and 30 normal fertile men as controls in group C. We detected Y chromosome microdeletion in different groups using multiplex PCR. Results: Y chromosome microdeletion was detected in 23(16. 8%) of the patients in group A, another 23(17. 0%) in group B,and 0 in group C. The rates of Y chromosome microdeletion were 22. 9% in group A1,10. 4% in group A2,20. 3% in group B1,and 13. 6% in group B2,and the microdeletion rate in the patients with severe oligozoospermia( groups A1 and B1) was 23. 3%(31 /133). No statistically significant difference was found between groups A and B( P > 0. 05). Conclusion: There are no significant differences in the rate of Y chromosome microdeletion between varicocele and non-varicocele patients with azoospermia or severe oligozoospermia, and Y chromosome microdeletion is one of the causes of azoospermia and severe oligozoospermia with varicocele.


Assuntos
Azoospermia/genética , Infertilidade Masculina/genética , Oligospermia/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Varicocele/complicações , Estudos de Casos e Controles , Deleção Cromossômica , Cromossomos Humanos Y/genética , Humanos , Incidência , Masculino , Aberrações dos Cromossomos Sexuais
13.
J Psycholinguist Res ; 43(3): 225-40, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23584838

RESUMO

The present study aimed to test the Sense Model of cross-linguistic masked translation priming asymmetry, proposed by Finkbeiner et al. (J Mem Lang 51:1-22, 2004), by manipulating the number of senses that bilingual participants associated with words from both languages. Three lexical decision experiments were conducted with Chinese-English bilinguals. In Experiment 1, polysemous L2 words and their L1 Chinese single-sense translation equivalents were selected as primes and targets. In Experiment 2, single-sense L1 words and their L2 translation equivalents with polysemous senses severed as primes and targets. We found translation priming effects in the L1-L2 direction, but not in the L2-L1 direction. In Experiment 3, presentation time of the L2 priming stimulus was prolonged, and significant translation priming effects were observed in the L2-L1 direction. These findings suggest that the Sense Model does not adequately explain cross-language translation priming asymmetry. The sense numbers of primes and targets, as well as the activation proportion of these senses between them, were possibly not the primary reason for cross-language translation priming asymmetry. The revised hierarchical model (Kroll and Stewart in J Mem Lang 33:149-174, 1994) and the BIA+ model (Dijkstra and van Heuven in Bilingualism Lang Cognit 5:175-197, 2002) better explain the cross-language translation priming asymmetry we found.


Assuntos
Idioma , Multilinguismo , Vocabulário , Cognição , Humanos , Modelos Teóricos , Traduções
14.
ACS Omega ; 9(31): 33448-33458, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39130570

RESUMO

The microbial enhanced oil recovery (MEOR) process has been identified as a promising alternative to conventional enhanced oil recovery methods because it is eco-friendly and economically advantageous. However, the knowledge about the composition and diversity of microbial communities in artificially regulated reservoirs, especially after activating petroleum hydrocarbon-degrading bacteria (PHDB) by injecting exogenous nutrients, is still insufficient. This study utilized a combination of high-throughput sequencing and metagenomics technology to reveal the structural evolution characteristics of the indigenous microbial community in the reservoir during the PHDB activated for enhanced oil recovery, as well as the response relationship between the expression of its oil production functional genes and crude oil biodegradation. Results showed that Pseudomonas (>75%) gradually evolves into a stable dominant microbial community in the reservoir during the activation of PHDB. Besides, the gene expression and KEGG pathways after crude oil undergoes biodegradation by PHDB show that the number of genes related to petroleum hydrocarbon metabolism dominates the metabolism (21.98%). Meanwhile, a preliminary schematic diagram was drawn to illustrate the evolution mechanism of the EOR metabolic pathway after the targeted activation of PHDB. Additionally, it was found that the abundance of hydrocarbon-degrading enzymes increased significantly, and the activity of alcohol dehydrogenase was higher than that of aldehyde dehydrogenase and monooxygenase after PHDB activation. These research results not only filled in and expanded the theoretical knowledge of MEOR based on artificial interference or regulation of reservoir oil-recovery functional microbial community structure but also provided guidance for the future application of MEOR technology in oil field operations.

15.
Research (Wash D C) ; 7: 0500, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39434838

RESUMO

Introduction: Brain age prediction using neuroimaging data and machine learning algorithms holds significant promise for gaining insights into the development of neurodegenerative diseases. The estimation of brain age may be influenced not only by the imaging modality but also by multidomain clinical factors. However, the degree to which various clinical factors in individuals are associated with brain structure, as well as the comprehensive relationship between these factors and brain aging, is not yet clear. Methods: In this study, multimodal brain magnetic resonance imaging data and longitudinal clinical information were collected from 964 participants in a population-based cohort with 16 years of follow-up in northern China. We developed a machine learning-based algorithm to predict multimodal brain age and compared the estimated brain age gap (BAG) differences among the 5 groups characterized by varying exposures to these high-risk clinical factors. We then estimated modality-specific brain age in the hypertension group based on hypertension-related regional imaging metrics. Results: The results revealed a significantly larger BAG estimated from multimodal neuroimaging in subjects with 4 or 5 risk factors compared to other groups, suggesting an acceleration of brain aging under cumulative exposure to multiple risk factors. The estimated T1-based BAG exhibited a significantly higher level in the hypertensive subjects compared to the normotensive individuals. Conclusion: Our study provides valuable insights into a range of health factors across lifestyle, metabolism, and social context that are reflective of brain aging and also contributes to the advancement of interventions and public health initiatives targeted at the general population aimed at promoting brain health.

16.
Int J Immunopathol Pharmacol ; 37: 3946320231181464, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37357623

RESUMO

The complement system is an important part of innate immunity. Through complement-dependent cytotoxicity (CDC), it plays an important role in the clearance of invading pathogens but also cancerous host cells. Therapy with anti-CD20 monoclonal antibodies (mAbs), for example, rituximab and ofatumumab, is a well-established treatment for lymphoid malignancies, and CDC is one of the main mechanisms underlying their anti-cancer activity. However, there are still some issues with the clinical application of anti-CD20 antibodies. On the one hand, anti-CD20 can cause some clinical side effects; on the other hand, anti-CD20 has low potency in some patients, and increasing the dosage does not enhance its effectiveness in these patients. Previous studies have reported that a gain-of-function in a certain complement component can boost the cytolytic activity of anti-CD20 mAbs. Through reviewing the literature on complement system control and anti-CD20 mAbs, this article aims to provide a thorough understanding of the potential of targeting complement components in lymphoma therapy.


Assuntos
Antineoplásicos , Linfoma , Humanos , Antígenos CD20 , Anticorpos Monoclonais/uso terapêutico , Rituximab/uso terapêutico , Proteínas do Sistema Complemento , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral
17.
Biomaterials ; 303: 122404, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37992600

RESUMO

Idiopathic pulmonary fibrosis (IPF) stands as a highly heterogeneous and deadly lung disease, yet the available treatment options remain limited. Combining myofibroblast inhibition with ROS modulation in damaged AECs offers a comprehensive strategy to halt IPF progression, but delivering drugs separately to these cell types is challenging. Inspired by the successful application of pulmonary surfactant (PS) replacement therapy in lung disease treatment, we have developed PS nano-biomimetic liposomes (PSBs) to utilize its natural transport pathway for targeting AECs while reducing lung tissue clearance. In this collaborative pulmonary drug delivery system, PSBs composed of DPPC/POPG/DPPG/CHO (20:9:5:4) were formulated for inhalation. These PSBs loaded with ROS-scavenger astaxanthin (AST) and anti-fibrosis drug pirfenidone (PFD) were aerosolized for precise quantification and mimicking patient inhalation. Through aerosol inhalation, the lipid membrane of PSBs gradually fused with natural PS, enabling AST delivery to AECs by hitchhiking with PS circulation. Simultaneously, PFD was released within the PS barrier, effectively penetrating lung tissue to exert therapeutic effects. In vivo results have shown that PSBs offer numerous therapeutic advantages in mice with IPF, particularly in terms of lung function recovery. This approach addresses the challenges of drug delivery to specific lung cells and offers potential benefits for IPF patients.


Assuntos
Fibrose Pulmonar Idiopática , Surfactantes Pulmonares , Humanos , Camundongos , Animais , Surfactantes Pulmonares/uso terapêutico , Surfactantes Pulmonares/metabolismo , Surfactantes Pulmonares/farmacologia , Lipossomos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Biomimética , Aerossóis e Gotículas Respiratórios , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/metabolismo , Piridonas/farmacologia
18.
ACS Omega ; 8(30): 27674-27687, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37546680

RESUMO

Aromatic maturity parameters were evaluated via closed-system pyrolysis experiments using a Mesozoic lacustrine source rock from the Yingen-Ejinaqi Basin, thereby ensuring a uniform source. Pulverized rock aliquots (200 mg) were reacted with water at temperatures ranging from 250 to 550 °C at 5 °C/min, and the aromatic fractions of expelled oil and extracts of the solid residue were analyzed by GC-MS. The experiments showed that the relative abundance of aromatic hydrocarbons in the oil and extractable organic matter (EOM) of source rock had different evolutionary characteristics. With the increase in the thermal evolution degree, the relative abundance of aromatic hydrocarbons in the EOM showed the characteristics of ″increased early (Ro < 0.80), unchanged middle (Ro = 0.80-2.00%), decreased lately (Ro > 2.00%)″. While the relative abundance of aromatic hydrocarbons in the expelled oils continuously increased, as the Ro values increased from 0.62 to 2.39%, the relative abundance of aromatic hydrocarbons gradually increased from 8 to 46%. With increased maturity, the relative abundance of 1-3-ring aromatic hydrocarbons continuously decreased, as observed in the phenanthrene homologs. Meanwhile, the relative abundance of 4+-ring aromatic hydrocarbons continuously increased, as seen in chrysene homologs. It was suggested that the effects of maturity on the composition of aromatic hydrocarbons might not be sufficiently obvious. The effective application range of the alkylnaphthalene-related maturity parameters (2-/1-methylnaphthalenes, (2,6- + 2,7-)/1,5-dimethylnaphthalenes, 2,3,6-/(1,4,6- + 1,3,5-) trimethylnaphthalenes, and (2,3,6- + 1,3,7-)/(1,4,6- + 1,3,5- + 1,3,6-) trimethylnaphthalenes) and the alkyldibenzothiophene maturity parameters (4-/1-methyldibenzothiophenes, 4,6-/(1,4- + 1,6-) dimethyldibenzothiophenes, and (2,6- + 3,6-)/(1,4- + 1,6-) dimethyldibenzothiophenes) was 0.84-2.06% Ro. The alkylphenanthrene-related maturity parameters had a wide application range for lacustrine source rocks with an Ro < 2.06%. These parameters included 1.5 × (2- + 3-)/(phenanthrene +1- + 9-) methylphenanthrenes, 3 × 2-/(phenanthrene + 1- + 9-) methylphenanthrenes, (2- + 3-)/(1- + 9-) methylphenanthrenes, 2-/1-methylphenanthrenes, (3- + 2-)/(1- + 2- + 3- + 9-) methylphenanthrenes, 2-/(1- + 2- + 3- + 9-) methylphenanthrenes, and 2,7-/1,8-dimethylphenanthrenes. In addition, the effective applicable range of the methylnaphthalene-related maturity parameter 3-/1-methylchrysenes was an Ro value less than 1.79%. The results clarified the validity scope of some aromatics' maturity parameters and provided a theoretical basis for the scientific application of these parameters.

19.
Zhongguo Zhong Yao Za Zhi ; 37(14): 2127-9, 2012 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-23126198

RESUMO

OBJECTIVE: To study the effect of Panax notoginseng saponins (PNS) on expression of alpha-aecretase mRNA in the brains of senescence-accelerated SAMP8 mice. METHOD: SAMP8 mice were randomly divided into the control group, the PNS high-dosage group (200 mg x kg(-1)), the PNS low-dosage group (100 mg x kg(-1)) and the huperzine A group (0.3 mg x kg(-1)), with eight mice in each group. The control group and each administration group were orally administered with the same volume of double distilled water once for consecutively two months. The expression of alpha-secretase (ADAM 9, ADAM10, ADAM17) mRNA was assayed by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). RESULT: The expression of ADAM9 mRNA in PNS high-dosage group and huperzine A group were significantly higher than that of the control group (P < 0.05). The expression of ADAM10 in the PNS high-dosage group, the PNS low-dosage group and the huperzine A group showed no significant difference from the control group. CONCLUSION: PNS can up-regulate expressions of ADAM9 mRNA and down-regulate expressions of ADAM10 mRNA in the brains of SAMP8 mice.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide/genética , Panax notoginseng , RNA Mensageiro/análise , Saponinas/farmacologia , Proteínas ADAM/genética , Proteína ADAM10 , Doença de Alzheimer/metabolismo , Animais , Modelos Animais de Doenças , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Proteínas de Membrana/genética , Camundongos
20.
BMJ Open ; 12(6): e060107, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35768082

RESUMO

OBJECTIVE: This study aimed to better understand the psychological experiences of inpatients with acute pancreatitis (AP). DESIGN: We used a qualitative descriptive study design to capture patients with AP's thoughts, feelings and behavioural responses. SETTING: We conducted this study in the gastroenterology departments of two tertiary hospitals in Eastern China. PARTICIPANTS: We used a convenience sampling approach to recruit 28 inpatients with AP from 1 August 2020 to 25 December 2020. The interviews were audio-recorded and transcribed verbatim. We employed an adapted version of Colaizzi's qualitative analysis approach to examine the data. RESULTS: We extracted three themes and eight subthemes regarding the participants' psychological experiences: (1) feeling that their disease is unpredictable (the inability to recognise the disease, uncertainty about the illness and fear of progression or recurrence); (2) various kinds of stress and support (feeling different degrees of stress, perceiving social support, seeking and craving social support); and (3) developing self-adaptability in the disease process (treating one's illness negatively or positively). CONCLUSIONS: Cognitive and emotional responses vary in patients with AP during hospitalisation. Moreover, patients with distinct conditions demonstrate significant differences in their responses and coping mechanisms. Healthcare providers need to mobilise social support and formulate comprehensive intervention strategies according to patients' individual characteristics.


Assuntos
Pacientes Internados , Pancreatite , Doença Aguda , Adaptação Psicológica , Humanos , Pancreatite/terapia , Pesquisa Qualitativa
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