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1.
Foods ; 13(18)2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39335827

RESUMO

Volatile organic compounds (VOCs) produced by Bacillus species exhibit biocontrol activity against fungal pathogens of fruits and vegetables. However, research on the effect of VOCs on Aspergillus flavus in stored grains is limited. This study aimed to investigate the effects of VOCs extracted from the strain R2, which was isolated from unhulled rice and identified as Bacillus paramycoides on A. flavus in vitro and unhulled rice. R2 VOCs effectively inhibited conidial germination and the hyphal growth of A. flavus in vitro. Moreover, R2 VOCs reduced the fungal population, aflatoxin B1 (AFB1) levels, and free fatty acid (FFA) value by 90.8%, 67%, and 38.7%, respectively, in unhulled rice. Eighteen R2 VOCs were identified using headspace solid-phase micro-extraction gas chromatography-mass spectrometry, and the individual activity of the VOCs against A. flavus was tested in vitro. Benzaldehyde (Ben) and 3,7-dimethyl-1-octanol (Dmo) showed strong inhibitory activities against A. flavus on PDA plates, with inhibition rates of 100% and 91.2%, respectively, at a concentration of 20 µL/dish. Ben at the concentration of 0.09 mg/mL, Dmo at the concentration of 0.07 mg/mL, or a mixture of both at halved concentrations could reduce the fungal population, AFB1 levels, and FFA content in unhulled rice. Our findings suggest that R2 VOCs are good alternatives to traditional chemical fumigants for suppressing A. flavus in stored grains. However, further research is necessary to establish the optimal fumigation concentration of these two components in unhulled rice. The impact of their residues on grain quality should be explored through sensory evaluation and nutritional analysis, and their safety to the environment and human body should be evaluated through safety assessment.

2.
Int J Biol Macromol ; 279(Pt 3): 135346, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39242010

RESUMO

This study was conducted to develop a W/O/W emulsion encapsulated Lactobacillus plantarum 23-1 (LP23-1) to significantly enhance the survival rate of LP23-1 under simulated digestion and storage conditions. The zein particles and pectin formed a complex through electrostatic interaction and hydrogen bonding. When the proportion of zein particles to pectin was 1:1, the emulsifying stability index (ESI) was 304.17 %. Additionally, when the proportion of the internal aqueous phase to the oil phase was 1:9, the polyglycerol polyricinoleate (PGPR) concentration was 5 %, the proportion of primary emulsion to the external aqueous phase was 5:5, the zein particles concentration was 4 %, and the proportion of zein particles to pectin was 1:1, the encapsulation rate was the highest at 96.27 %. Cryo-scanning electron microscopy and fluorescence microscopy confirmed the morphology of W/O/W emulsion and successful encapsulation of LP23-1. Furthermore, compared with free LP23-1, the W/O/W emulsion encapsulation significantly improved the survival rate of LP23-1 to 73.36 % after simulated gastrointestinal digestion and maintained a high survival rate of 78.42 % during the 35-day storage. The W/O/W emulsion was found to effectively improve the survival rate of LP23-1 during simulated digestion and storage, which has implications for the development of probiotic functional foods with elevated survival rates.


Assuntos
Emulsões , Lactobacillus plantarum , Pectinas , Zeína , Pectinas/química , Zeína/química , Probióticos , Tamanho da Partícula , Água/química , Viabilidade Microbiana/efeitos dos fármacos , Glicerol/análogos & derivados , Ácidos Ricinoleicos
3.
Front Cardiovasc Med ; 11: 1435106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39318836

RESUMO

Background: Peripheral Artery Disease (PAD) is a common vascular disorder typically caused by atherosclerosis, leading to impaired blood supply to the lower extremities, resulting in pain, necrosis, and even amputation. Despite extensive research into the pathogenesis of PAD, many mysteries remain, particularly regarding its association with human blood metabolites. Methods: To explore the causal relationship between 1,400 serum metabolites and PAD, a two-sample Mendelian randomization (MR) analysis was conducted. The Inverse Variance-Weighted (IVW) method was the primary technique used to estimate the causal impact of the metabolites on PAD. To enhance the analysis, several additional methods were employed: MR-Egger regression, weighted median, simple mode, and weighted mode. These methods provided a comprehensive evaluation beyond the primary IVW estimation. To ensure the validity of the MR findings, sensitivity analysis was performed. Furthermore, a bidirectional MR approach was applied to explore the possibility of a reverse causal effect between PAD and potential candidate metabolites. Results: After rigorous selection, significant associations were found between 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (p-18:0/20:4) and X-17653 levels with PAD. 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (p-18:0/20:4) was positively associated with increased PAD risk (IVW OR = 1.13, 95% CI, 1.06-1.21; P < 0.001). X-17653 levels were associated with decreased PAD risk (IVW OR = 0.88, 95% CI, 0.83-0.94; P < 0.001). In the reverse direction, PAD was positively associated with increased 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (p-18:0/20:4) levels (IVW OR = 1.16, 95% CI, 1.01-1.34; P = 0.036). PAD was not associated with X-17653. Conclusion: Among 1,400 blood metabolites, 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (p-18:0/20:4) and X-17653 are significantly associated with PAD risk. Importantly, in the reverse direction, PAD was found to be positively associated with increased levels of 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (p-18:0/20:4). This highlights the bidirectional nature of the association and suggests a potential feedback mechanism between PAD and this specific lipid species. 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (p-18:0/20:4) may serve as potential biomarkers for PAD, aiding early diagnosis and providing novel avenues for personalized treatment and management. However, further validation and research are warranted despite the promising results.

4.
Cogn Neurodyn ; 18(4): 1895-1911, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39104680

RESUMO

Dopamine modulates working memory in the prefrontal cortex (PFC) and is crucial for obsessive-compulsive disorder (OCD). However, the mechanism is unclear. Here we establish a biophysical model of the effect of dopamine (DA) in PFC to explain the mechanism of how high dopamine concentrations induce persistent neuronal activities with the network plunging into a deep, stable attractor state. The state develops a defect in working memory and tends to obsession and compulsion. Weakening the reuptake of dopamine acts on synaptic plasticity according to Hebbian learning rules and reward learning, which in turn affects the strength of neuronal synaptic connections, resulting in the tendency of compulsion and learned obsession. In addition, we elucidate the potential mechanisms of dopamine antagonists in OCD, indicating that dopaminergic drugs might be available for treatment, even if the abnormality is a consequence of glutamate hypermetabolism rather than dopamine. The theory highlights the significance of early intervention and behavioural therapies for obsessive-compulsive disorder. It potentially offers new approaches to dopaminergic pharmacotherapy and psychotherapy for OCD patients.

5.
Int J Nanomedicine ; 19: 7817-7830, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39099790

RESUMO

Background: Photothermal therapy (PTT) guided by photoacoustic imaging (PAI) using nanoplatforms has emerged as a promising strategy for cancer treatment due to its efficiency and accuracy. This study aimed to develop and synthesize novel second near-infrared region (NIR-II) absorption-conjugated polymer acceptor acrylate-substituted thiadiazoloquinoxaline-diketopyrrolopyrrole polymers (PATQ-DPP) designed specifically as photothermal and imaging contrast agents for nasopharyngeal carcinoma (NPC). Methods: The PATQ-DPP nanoparticles were synthesized and characterized for their optical properties, including low optical band gaps. Their potential as PTT agents and imaging contrast agents for NPC was evaluated both in vitro and in vivo. The accumulation of nanoparticles at tumor sites was assessed post-injection, and the efficacy of PTT under near-infrared laser irradiation was investigated in a mouse model of NPC. Results: Experimental results indicated that the PATQ-DPP nanoparticles exhibited significant photoacoustic contrast enhancement and favorable PTT performance. Safety and non-toxicity evaluations confirmed the biocompatibility of these nanoparticles. In vivo studies showed that PATQ-DPP nanoparticles effectively accumulated at NPC tumor sites and demonstrated excellent tumor growth inhibition upon exposure to near-infrared laser irradiation. Notably, complete elimination of nasopharyngeal tumors was observed within 18 days following PTT. Discussion: The findings suggest that PATQ-DPP nanoparticles are a promising theranostic agent for NIR-II PAI and PTT of tumors. This innovative approach utilizing PATQ-DPP nanoparticles provides a powerful tool for the early diagnosis and precise treatment of NPC, offering a new avenue in the management of this challenging malignancy.


Assuntos
Nanopartículas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Técnicas Fotoacústicas , Terapia Fototérmica , Animais , Técnicas Fotoacústicas/métodos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/diagnóstico por imagem , Terapia Fototérmica/métodos , Camundongos , Linhagem Celular Tumoral , Humanos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/diagnóstico por imagem , Nanopartículas/química , Raios Infravermelhos , Camundongos Nus , Meios de Contraste/química , Camundongos Endogâmicos BALB C , Polímeros/química , Feminino
6.
Neural Netw ; 178: 106422, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38901095

RESUMO

Locomotion and scratching are basic motor functions which are critically important for animal survival. Although the spinal circuits governing forward locomotion have been extensively investigated, the organization of spinal circuits and neural mechanisms regulating backward locomotion and scratching remain unclear. Here, we extend a model by Danner et al. to propose a spinal circuit model with asymmetrical cervical-lumbar layout to investigate these issues. In the model, the left-right alternation within the cervical and lumbar circuits is mediated by V 0D and V 0V commissural interneurons (CINs), respectively. With different control strategies, the model closely reproduces multiple experimental data of quadrupeds in different motor behaviors. Specifically, under the supraspinal drive, walk and trot are expressed in control condition, half-bound is expressed after deletion of V 0V CINs, and bound is expressed after deletion of V0 (V 0D and V 0V) CINs; in addition, unilateral hindlimb scratching occurs in control condition and synchronous bilateral hindlimb scratching appears after deletion of V 0V CINs. Under the combined drive of afferent feedback and perineal stimulation, different coordination patterns between hindlimbs during BBS (backward-biped-spinal) locomotion are generated. The results suggest that (1) the cervical and lumbar circuits in the spinal network are asymmetrically recruited during particular rhythmic limb movements. (2) Multiple motor behaviors share a single spinal network under the reconfiguration of the spinal network by supraspinal inputs or somatosensory feedback. Our model provides new insights into the organization of motor circuits and neural control of rhythmic limb movements.


Assuntos
Interneurônios , Locomoção , Medula Espinal , Locomoção/fisiologia , Animais , Interneurônios/fisiologia , Medula Espinal/fisiologia , Modelos Neurológicos , Membro Posterior/fisiologia
7.
Cereb Cortex ; 34(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38904079

RESUMO

Serotonin (5-HT) regulates working memory within the prefrontal cortex network, which is crucial for understanding obsessive-compulsive disorder. However, the mechanisms how network dynamics and serotonin interact in obsessive-compulsive disorder remain elusive. Here, we incorporate 5-HT receptors (5-HT1A, 5-HT2A) and dopamine receptors into a multistable prefrontal cortex network model, replicating the experimentally observed inverted U-curve phenomenon. We show how the two 5-HT receptors antagonize neuronal activity and modulate network multistability. Reduced binding of 5-HT1A receptors increases global firing, while reduced binding of 5-HT2A receptors deepens attractors. The obtained results suggest reward-dependent synaptic plasticity mechanisms may attenuate 5-HT related network impairments. Integrating serotonin-mediated dopamine release into circuit, we observe that decreased serotonin concentration triggers the network into a deep attractor state, expanding the domain of attraction of stable nodes with high firing rate, potentially causing aberrant reverse learning. This suggests a hypothesis wherein elevated dopamine concentrations in obsessive-compulsive disorder might result from primary deficits in serotonin levels. Findings of this work underscore the pivotal role of serotonergic dysregulation in modulating synaptic plasticity through dopamine pathways, potentially contributing to learned obsessions. Interestingly, serotonin reuptake inhibitors and antidopaminergic potentiators can counteract the over-stable state of high-firing stable points, providing new insights into obsessive-compulsive disorder treatment.


Assuntos
Transtorno Obsessivo-Compulsivo , Córtex Pré-Frontal , Serotonina , Córtex Pré-Frontal/metabolismo , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/metabolismo , Serotonina/metabolismo , Humanos , Dopamina/metabolismo , Modelos Neurológicos , Receptores Dopaminérgicos/metabolismo , Rede Nervosa/metabolismo , Rede Nervosa/fisiopatologia , Simulação por Computador , Receptor 5-HT2A de Serotonina/metabolismo , Receptores de Serotonina/metabolismo , Plasticidade Neuronal/fisiologia , Receptor 5-HT1A de Serotonina/metabolismo
8.
J Phys Chem A ; 128(27): 5243-5252, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38937149

RESUMO

Direct methanol fuel cells (DMFCs) have attracted increasing attention as a very promising and important energy source. In this paper, density functional theory (DFT) is used to study the structure and O-H fracture mechanism of methanol adsorption on PtnCu4-n (111) (n = 1, 2, 3) binary metal catalyst surfaces under different coverages. By comparing the adsorption energy and dehydrogenation energy barriers of methanol, it is found that the adsorption strength and dehydrogenation energy barriers of methanol on Pt and Cu sites decreased with increasing coverage. At the same Pt and Cu ratio, methanol is more easily adsorbed on Cu sites. When Pt/Cu = 3:1 and 1:3, the PtCu binary catalyst has a significant impact on the energy barrier of breaking the O-H bond in methanol with the increase of coverage. Especially when Pt/Cu = 1:3 and the coverage is 1/4 ML, the energy barriers of O-H bond breaking in methanol on Pt and Cu sites are 0.63 and 0.61 eV, respectively, which are lower than that on pure Pt. It means that the Cu sites played a very important role in reducing the O-H fracture energy barrier of methanol. When Pt/Cu = 1:1, the change in the dehydrogenation energy barrier of methanol on Pt sites and Cu sites is not significant, indicating that the coverage has little effect on it.

9.
Biomimetics (Basel) ; 9(6)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38921194

RESUMO

The objective of this research is to achieve biologically autonomous control by utilizing a whole-brain network model, drawing inspiration from biological neural networks to enhance the development of bionic intelligence. Here, we constructed a whole-brain neural network model of Caenorhabditis elegans (C. elegans), which characterizes the electrochemical processes at the level of the cellular synapses. The neural network simulation integrates computational programming and the visualization of the neurons and synapse connections of C. elegans, containing the specific controllable circuits and their dynamic characteristics. To illustrate the biological neural network (BNN)'s particular intelligent control capability, we introduced an innovative methodology for applying the BNN model to a 12-legged robot's movement control. Two methods were designed, one involving orientation control and the other involving locomotion generation, to demonstrate the intelligent control performance of the BNN. Both the simulation and experimental results indicate that the robot exhibits more autonomy and a more intelligent movement performance under BNN control. The systematic approach of employing the whole-brain BNN for robot control provides biomimetic research with a framework that has been substantiated by innovative methodologies and validated through the observed positive outcomes. This method is established as follows: (1) two integrated dynamic models of the C. elegans' whole-brain network and the robot moving dynamics are built, and all of the controllable circuits are discovered and verified; (2) real-time communication is achieved between the BNN model and the robot's dynamical model, both in the simulation and the experiments, including applicable encoding and decoding algorithms, facilitating their collaborative operation; (3) the designed mechanisms using the BNN model to control the robot are shown to be effective through numerical and experimental tests, focusing on 'foraging' behavior control and locomotion control.

10.
mSystems ; 9(6): e0138523, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38752789

RESUMO

A dysfunction of human host genes and proteins in coronavirus infectious disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key factor impacting clinical symptoms and outcomes. Yet, a detailed understanding of human host immune responses is still incomplete. Here, we applied RNA sequencing to 94 samples of COVID-19 patients with and without hematological tumors as well as COVID-19 uninfected non-tumor individuals to obtain a comprehensive transcriptome landscape of both hematological tumor patients and non-tumor individuals. In our analysis, we further accounted for the human-SARS-CoV-2 protein interactome, human protein interactome, and human protein complex subnetworks to understand the mechanisms of SARS-CoV-2 infection and host immune responses. Our data sets enabled us to identify important SARS-CoV-2 (non-)targeted differentially expressed genes and complexes post-SARS-CoV-2 infection in both hematological tumor and non-tumor individuals. We found several unique differentially expressed genes, complexes, and functions/pathways such as blood coagulation (APOE, SERPINE1, SERPINE2, and TFPI), lipoprotein particle remodeling (APOC2, APOE, and CETP), and pro-B cell differentiation (IGHM, VPREB1, and IGLL1) during COVID-19 infection in patients with hematological tumors. In particular, APOE, a gene that is associated with both blood coagulation and lipoprotein particle remodeling, is not only upregulated in hematological tumor patients post-SARS-CoV-2 infection but also significantly expressed in acute dead patients with hematological tumors, providing clues for the design of future therapeutic strategies specifically targeting COVID-19 in patients with hematological tumors. Our data provide a rich resource for understanding the specific pathogenesis of COVID-19 in immunocompromised patients, such as those with hematological malignancies, and developing effective therapeutics for COVID-19. IMPORTANCE: A majority of previous studies focused on the characterization of coronavirus infectious disease 2019 (COVID-19) disease severity in people with normal immunity, while the characterization of COVID-19 in immunocompromised populations is still limited. Our study profiles changes in the transcriptome landscape post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hematological tumor patients and non-tumor individuals. Furthermore, our integrative and comparative systems biology analysis of the interactome, complexome, and transcriptome provides new insights into the tumor-specific pathogenesis of COVID-19. Our findings confirm that SARS-CoV-2 potentially tends to target more non-functional host proteins to indirectly affect host immune responses in hematological tumor patients. The identified unique genes, complexes, functions/pathways, and expression patterns post-SARS-CoV-2 infection in patients with hematological tumors increase our understanding of how SARS-CoV-2 manipulates the host molecular mechanism. Our observed differential genes/complexes and clinical indicators of normal/long infection and deceased COVID-19 patients provide clues for understanding the mechanism of COVID-19 progression in hematological tumors. Finally, our study provides an important data resource that supports the increasing value of the application of publicly accessible data sets to public health.


Assuntos
COVID-19 , Hospedeiro Imunocomprometido , SARS-CoV-2 , Transcriptoma , Humanos , COVID-19/genética , COVID-19/imunologia , COVID-19/virologia , Transcriptoma/genética , SARS-CoV-2/genética , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Masculino , Feminino , Mapas de Interação de Proteínas/genética , Pessoa de Meia-Idade , Perfilação da Expressão Gênica/métodos
11.
Eur J Neurosci ; 60(3): 4224-4243, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38812400

RESUMO

Stimulus size modulation of neuronal firing activity is a fundamental property of the primary visual cortex. Numerous biological experiments have shown that stimulus size modulation is affected by multiple factors at different spatiotemporal scales, but the exact pathways and mechanisms remain incompletely understood. In this paper, we establish a large-scale neuronal network model of primary visual cortex with layer 2/3 to study how gamma oscillation properties are modulated by stimulus size and especially how long-range connections affect the modulation as realistic neuronal properties and spatial distributions of synaptic connections are considered. It is shown that long-range horizontal synaptic connections are sufficient to produce dimensional modulation of firing rates and gamma oscillations. In particular, with increasing grating stimulus size, the firing rate increases and then decreases, the peak frequency of gamma oscillations decreases and the spectral power increases. These are consistent with biological experimental observations. Furthermore, we explain in detail how the number and spatial distribution of long-range connections affect the size modulation of gamma oscillations by using the analysis of neuronal firing activity and synaptic current fluctuations. Our results provide a mechanism explanation for size modulation of gamma oscillations in the primary visual cortex and reveal the important and unique role played by long-range connections, which contributes to a deeper understanding of the cognitive function of gamma oscillations in visual cortex.


Assuntos
Ritmo Gama , Modelos Neurológicos , Neurônios , Córtex Visual Primário , Ritmo Gama/fisiologia , Córtex Visual Primário/fisiologia , Animais , Neurônios/fisiologia , Humanos , Rede Nervosa/fisiologia , Córtex Visual/fisiologia , Potenciais de Ação/fisiologia
12.
Cell Signal ; 118: 111135, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38479555

RESUMO

BACKGROUND: Pancreatic fibrosis is one of the most important pathological features of chronic pancreatitis (CP) and pancreatic stellate cells (PSCs) are the key cells of fibrosis. As an extracellular matrix (ECM) glycoprotein, cartilage oligomeric matrix protein (COMP) is critical for collagen assembly and ECM stability and recent studies showed that COMP exert promoting fibrosis effect in the skin, lungs and liver. However, the role of COMP in activation of PSCs and pancreatic fibrosis remain unclear. We aimed to investigate the role and specific mechanisms of COMP in regulating the profibrotic phenotype of PSCs and pancreatic fibrosis. METHODS: ELISA method was used to determine serum COMP in patients with CP. Mice model of CP was established by repeated intraperitoneal injection of cerulein and pancreatic fibrosis was evaluated by Hematoxylin-Eosin staining (H&E) and Sirius red staining. Immunohistochemical staining was used to detect the expression changes of COMP and fibrosis marker such as α-SMA and Fibronectin in pancreatic tissue of mice. Cell Counting Kit-8, Wound Healing and Transwell assessed the proliferation and migration of human pancreatic stellate cells (HPSCs). Western blotting, qRT-PCR and immunofluorescence staining were performed to detect the expression of fibrosis marker, AKT and MAPK family proteins in HPSCs. RNA-seq omics analysis as well as small interfering RNA of COMP, recombinant human COMP (rCOMP), MEK inhibitors and PI3K inhibitors were used to study the effect and mechanism of COMP on activation of HPSCs. RESULTS: ELISA showed that the expression of COMP significantly increased in the serum of CP patients. H&E and Sirius red staining analysis showed that there was a large amount of collagen deposition in the mice in the CP model group and high expression of COMP, α-SMA, Fibronectin and Vimentin were observed in fibrotic tissues. TGF-ß1 stimulates the activation of HPSCs and increases the expression of COMP. Knockdown of COMP inhibited proliferation and migration of HPSCs. Further, RNA-seq omics analysis and validation experiments in vitro showed that rCOMP could significantly promote the proliferation and activation of HPSCs, which may be due to promoting the phosphorylation of ERK and AKT through membrane protein receptor CD36. rCOMP simultaneously increased the expression of α-SMA, Fibronectin and Collagen I in HPSCs. CONCLUSION: In conclusion, this study showed that COMP was up-regulated in CP fibrotic tissues and COMP induced the activation, proliferation and migration of PSCs through the CD36-ERK/AKT signaling pathway. COMP may be a potential therapeutic candidate for the treatment of CP. Interfering with the expression of COMP or the communication between COMP and CD36 on PSCs may be the next direction for therapeutic research.


Assuntos
Pancreatopatias , Pancreatite Crônica , Animais , Humanos , Camundongos , Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Proteína de Matriz Oligomérica de Cartilagem/farmacologia , Proteína de Matriz Oligomérica de Cartilagem/uso terapêutico , Células Cultivadas , Colágeno Tipo I/metabolismo , Fibronectinas/metabolismo , Fibrose , Pancreatopatias/metabolismo , Células Estreladas do Pâncreas/metabolismo , Células Estreladas do Pâncreas/patologia , Pancreatite Crônica/tratamento farmacológico , Pancreatite Crônica/metabolismo , Pancreatite Crônica/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
13.
Autoimmun Rev ; 23(4): 103530, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38499168

RESUMO

BACKGROUND: Formation of anti-drug antibodies (ADAs) against biologics is an important cause of psoriasis treatment failure. OBJECTIVE: This study aimed to summarize the characteristics of ADAs formation under different biological therapies and the influence of ADAs on the clinical effects and safety of biologics in patients with psoriasis. METHODS: PubMed, Embase, and Web of Science databases were searched from their inception to August 2022. Studies on biologics that assessed ADA levels in patients with psoriasis were included. The Cochrane risk-of-bias tool was used to assess the quality of randomized controlled trials (RCTs), the Newcastle-Ottawa Quality Assessment Scale (NOS) for case-control and cohort studies, and the Joanna Briggs Institute (JBI) critical appraisal checklist for single-arm studies. We calculated the pooled incidence with a random-effects model using R software. Subgroup analyses revealed that differences in patient characteristics, disease conditions, study design, and immunoassays may influence ADA generation and detection. RESULTS: The analysis included 86 studies, with a total population of 42,280 individuals. The pooled ADA rates were 0.49%, 2.20%, 2.38%, 4.08%, 7.38%, 7.94%, 14.29%, 21.93%, 29.70%, 31.76%, and 39.58% for secukinumab, etanercept, brodalumab, ustekinumab, tildrakizumab, guselkumab, ixekizumab, risankizumab, infliximab, adalimumab, and bimekizumab, respectively. >70% (95% CI, 0.71-0.81) of ADAs against adalimumab were neutralizing antibodies, and over 70% of ADAs against secukinumab and brodalumab were transient. Concomitant methotrexate therapy with tumor necrosis factor-α (TNF-α) inhibitors decreased ADA levels. Lower infliximab doses and intermittent therapy with interleukin (IL)-23 p19 inhibitors increased ADA formation. Additionally, ADA formation under treatment using TNF-α inhibitors and IL-12/23 p40 inhibitors was associated with lower response rates or serum drug levels, but only high ADA titers reduced the clinical effects of IL-17 inhibitors. The occurrence of IL-23 p19 and TNF-α inhibitors has been linked to injection-site reactions. CONCLUSIONS: Among the 11 biologics, secukinumab, etanercept, and brodalumab resulted in the lowest ADA formation rates. Immunogenicity contributes to lower biological efficacy and a higher likelihood of injection-site reactions. Low doses, intermittent treatment may increase ADA formation. An appropriate biologic should be selected based on the ADA formation rate and course of treatment.


Assuntos
Produtos Biológicos , Psoríase , Psoríase/imunologia , Psoríase/tratamento farmacológico , Humanos , Produtos Biológicos/uso terapêutico , Produtos Biológicos/imunologia , Produtos Biológicos/efeitos adversos , Anticorpos/imunologia , Anticorpos/sangue
15.
Altern Ther Health Med ; 30(10): 244-249, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38330575

RESUMO

Objective: The objective of this study was to assess the effectiveness of fecal collection devices in preventing incontinence-associated dermatitis (IAD) and reducing skin care time in ICU patients with fecal incontinence undergoing Extracorporeal Membrane Oxygenation (ECMO). Methods: A nonrandomized comparison cohort (quasi-experimental) study with pre-post comparison was carried out in a general intensive care unit. 85 bedridden patients receiving ECMO with fecal incontinence (FI) in a general intensive care unit between June 2017 and May 2022 participated in the study and separated into two groups according to the fecal collection device they received. 40 were assigned to the Control group (structured IAD preventive care protocol alone) and 45 to the Intervention group (structured IAD preventive care protocol plus application of fecal collection device). The status of IAD was assessed using the Incontinence Associated Dermatitis Intervention Tool (IAD-IT). Fecal consistency was evaluated via the Bristol Stool Scale. Outcome measures included the nursing time for skin care and the incidence of IAD, and bleeding complications between the two groups during the period. Results: Participants in the Intervention group had fewer IAD occurrences than participants in the Control group (13.33% vs. 52.50%, P < .05). The patients in the Intervention group significantly reduced skincare time (63.30±14.09 min in the Control group versus 28.44±2.04 min in the Intervention group, P < .01). There was 3 turning complications for bleeding in the Intervention group and 11 in the Control group and had a significant reduction in urning complications(3 vs.11, P = .022). Conclusions: Applying a fecal collection device may reduce skincare time and reduce occurrences of IAD and bleeding related to turning position for skin care in ICU patients with FI associated with diarrhea receiving ECMO Support.This study offers a more efficient way to use the fecal collection device in ECMO patients.Future research needs to focus on the perianal skin in ECMO patients regarding fecal collection devices connected to continuous low-negative-pressure suction devices.


Assuntos
Oxigenação por Membrana Extracorpórea , Incontinência Fecal , Unidades de Terapia Intensiva , Humanos , Incontinência Fecal/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos de Coortes , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Adulto , Idoso , Dermatite/terapia , Dermatite/etiologia
16.
Brain Res Bull ; 207: 110879, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38237873

RESUMO

Due to the complexity of focal epilepsy and its risk for transiting to the generalized epilepsy, the development of reliable classification methods to accurately predict and classify focal and generalized seizures is critical for the clinical management of patients with epilepsy. In order to holistically understand the seizure propagation behavior of focal epilepsy, we propose a three-node motif reduced network by respectively simplifying the focal region, surrounding healthy region and their critical regions as the single node. Because three-node motif can richly characterize information evolutions, the motif analysis method could comprehensively investigate the seizure behavior of focal epilepsy. Firstly, we define a new seizure propagation marker value to capture the seizure onsets and intensity. Based on the three-node motif analysis, it is shown that the focal seizure and spreading can be categorized as inhibitory seizure, focal seizure, focal-critical seizure and generalized seizures, respectively. The four types of seizures correspond to specific modal types respectively, reflecting the strong correlation between seizure behavior and information flow evolution. In addition, it is found that the intensity difference of outflow and inflow information from the critical node (connection heterogeneity) and the excitability of the critical node significantly affected the distribution and transition of the four seizure types. In particular, the method of local linear stability analysis also verifies the effectiveness of four types of seizures classification. In sum, this paper computationally confirms the complex dynamic behavior of focal seizures, and the study of criticality is helpful to propose novel seizure control strategies.


Assuntos
Epilepsias Parciais , Epilepsia , Transtornos Mentais , Humanos , Convulsões/diagnóstico , Convulsões/etiologia , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/complicações , Epilepsia/complicações , Eletroencefalografia
17.
Ann Hematol ; 103(1): 153-162, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37749319

RESUMO

The purpose is to ascertain the clinical impact of Castleman disease (CD) by reassessment of the real-world data from Peking University First Hospital (PKUFH). The results will contribute to the standardization of diagnosis and treatment on CDs. Based on the last 15-year retrospective real-world data from Peking University First Hospital (PKUFH), we reclassified and re-evaluated the clinical and pathological information of patients with pathologically suspected diagnosis of CD. A total of 203 patients were included in our study, in which the diagnosis of CD was confirmed in 189 cases, including 118 patients with unicentric CD (UCD, n = 118, 62.4%) and 71 patients with multicentric CD (MCD, n = 71, 37.6%). A total of 44.1% (n = 52) of UCDs in our cohort were complicated with paraneoplastic pemphigus (PNP). The treatment of UCD is primarily surgical, with a 5-year overall survival (OS) of 88.1%. Patients with PNP had a poorer prognosis than those without PNP (82.9% (95% CI 123-178) vs 92.8% (95% CI 168-196), log-rank p = 0.041). The rate of concurrent systemic symptoms was 74.6% (n = 53), and renal involvement occurred in 49.3% (n = 35) MCD patients. The MCD treatments were mainly chemotherapy regimens, with a 5-year OS of 77.6% (95% CI, 143-213). Patients with UCD demonstrate a better overall prognosis than patients with MCD. But the prognosis of those complicated with PNP was poor. The differential diagnosis of MCD is extensive. MCD treatment in China is heterogeneous. The inaccessibility of anti-IL-6-targeted drugs in China may contribute to the poor prognosis for patients with MCD.A preprint has previously been published (Guo et al. 34).


Assuntos
Hiperplasia do Linfonodo Gigante , Humanos , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/epidemiologia , Hiperplasia do Linfonodo Gigante/terapia , Estudos Retrospectivos , Pequim/epidemiologia , Prognóstico , China/epidemiologia
18.
Molecules ; 28(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38067587

RESUMO

The co-gasification of biomass and coal is helpful for achieving the clean and efficient utilization of phosphorus-rich biomass. A large number of alkali and alkaline earth metals (AAEMs) present in the ash system of coal (or biomass) cause varying degrees of ash, slagging, and corrosion problems in the entrained flow gasifier. Meanwhile, phosphorus is present in the slag in the form of PO43-, which has a strong affinity for AAEMs (especially for Ca2+) to produce minerals dominated by calcium phosphates or alkaline Ca-phosphate, effectively mitigating the aforementioned problems. To investigate the changing behavior of the slag flow temperature (FT) under different CaO/P2O5 ratios, 72 synthetic ashes with varying CaO/P2O5 ratios at different Si/Al contents and compositions were prepared, and their ash fusion temperatures were tested. The effects of different CaO/P2O5 ratios on the FT were analyzed using FactSage thermodynamic simulation. A model for predicting slag FT at different CaO/P2O5 ratios was constructed on the basis of the average molar ionic potential (Ia) method and used to predict data reported from 19 mixed ashes in the literature. The results showed that Ia and FT gradually increased with a decreasing CaO/P2O5 ratio, and the main mineral types shifted from anorthite → mullite → berlinite, which reasonably explained the decrease in ash fusion temperatures in the mixed ash. The established model showed good adaptability to the prediction of 19 actual coal ash FTs in the literature; the deviation of the prediction was in the range of 40 °C. The model proposed between FT and Ia based on the different CaO/P2O5 ratios can be used to predict the low-rank coal and phosphorus-rich biomass and their mixed ashes.

19.
Front Immunol ; 14: 1274492, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928518

RESUMO

Background: The widespread adoption of Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) has significantly improved the survival rates of patients with hematological malignancies. However, Graft-Versus-Host Disease (GVHD) remains a formidable complication, threatening patient prognosis. Recent research has indicated that decitabine (DAC), known for its hypomethylating properties may also exhibit immune-regulatory capabilities and a potential for reducing GVHD incidence and enhancing survival. Methods: We retrospectively reviewed data from AML/MDS patients who underwent Allo-HSCT at our center from January 2010 to January 2023. From a total of 251 patients with complete data, we employed propensity score matching (PSM) to create 100 matched pairs (200 patients) for comprehensive trial analysis. Patients receiving low-dose DAC-containing regimen were matched with those who did not receive DAC. Results: Patients in the DAC group exhibited a significantly lower incidence of grade II-IV acute GVHD (aGVHD) compared to non-DAC group (21% vs. 38%, P=0.013). Univariable and multivariable logistic regression analysis demonstrated DAC intervention as a protective factor against grade II-IV aGVHD (P=0.017, OR=0.47, 95% CI 0.23-0.81; P=0.018, OR=0.46, 95% CI 0.24-0.87). Multivariate competing risk regression further supported administration of decitabine as a protective factor against grade II-IV aGVHD (P=0.038, SHR=0.53, 95%CI 0.29-0.97). There was no significant difference between both groups concerning chronic GVHD, infection, disease relapse, overall survival, disease-free survival and GVHD free, relapse free survival. In MRD negative or intermediate risk subgroup, the grade II-IV aGVHD ameliorating effect of DAC was confirmed as well. Conclusion: Low-dose DAC-intensified modified conditioning regimen could improve prognosis in AML/MDS Patients treated with allogeneic hematopoietic stem cell transplantation.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Decitabina/uso terapêutico , Estudos Retrospectivos , Transplante Homólogo , Recidiva Local de Neoplasia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia Mieloide Aguda/patologia
20.
Phys Rev E ; 108(4-1): 044402, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37978611

RESUMO

Cognition involves the global integration of distributed brain regions that are known to work cohesively as cognitive subsystems during brain functioning. Empirical evidence has suggested that spatiotemporal phase relationships between brain regions, measured as synchronization and metastability, may encode important task-relevant information. However, it remains largely unknown how phase relationships aggregate at the level of cognitive subsystems under different cognitive processing. Here, we probe this question by simulating task-relevant brain dynamics through regional stimulation of a whole-brain dynamical network model operating in the resting-state dynamical regime. The model is constructed with structurally embedded Stuart-Laudon oscillators and then fitted with human resting-state functional magnetic resonance imaging data. Based on this framework, we first demonstrate the plausibility of introducing the cognitive system partition into the modeling analysis framework by showing that the clustering of regions across functional networks is better circumscribed by the predefined partition. At the cognitive subsystem level, we focus on how task-relevant phase dynamics are organized in terms of synchronization and metastability. We found that patterns of cognitive synchronization are more task specific, whereas patterns of cognitive metastability are more consistent across different states, suggesting it may encode a more task-general property during cognitive processing, an inherent property conferred by brain organization. This consistent network architecture in cognitive metastability may be related to the distinct functional responses of realistic cognitive systems. We also provide empirical evidence to partially support our computational results. Our paper may provide insights for the mechanisms underlying task-relevant brain dynamics, and establish a model-based link between brain structure, dynamics, and cognition, a fundamental step for computationally aided brain interventions.


Assuntos
Encéfalo , Rede Nervosa , Humanos , Rede Nervosa/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Cognição/fisiologia , Mapeamento Encefálico , Análise por Conglomerados
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