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1.
BMC Womens Health ; 24(1): 380, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956552

RESUMO

BACKGROUND: The aim of this study is to assess the efficacy of a multiparametric ultrasound imaging omics model in predicting the risk of postoperative recurrence and molecular typing of breast cancer. METHODS: A retrospective analysis was conducted on 534 female patients diagnosed with breast cancer through preoperative ultrasonography and pathology, from January 2018 to June 2023 at the Affiliated Cancer Hospital of Xinjiang Medical University. Univariate analysis and multifactorial logistic regression modeling were used to identify independent risk factors associated with clinical characteristics. The PyRadiomics package was used to delineate the region of interest in selected ultrasound images and extract radiomic features. Subsequently, radiomic scores were established through Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support Vector Machine (SVM) methods. The predictive performance of the model was assessed using the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was calculated. Evaluation of diagnostic efficacy and clinical practicability was conducted through calibration curves and decision curves. RESULTS: In the training set, the AUC values for the postoperative recurrence risk prediction model were 0.9489, and for the validation set, they were 0.8491. Regarding the molecular typing prediction model, the AUC values in the training set and validation set were 0.93 and 0.92 for the HER-2 overexpression phenotype, 0.94 and 0.74 for the TNBC phenotype, 1.00 and 0.97 for the luminal A phenotype, and 1.00 and 0.89 for the luminal B phenotype, respectively. Based on a comprehensive analysis of calibration and decision curves, it was established that the model exhibits strong predictive performance and clinical practicability. CONCLUSION: The use of multiparametric ultrasound imaging omics proves to be of significant value in predicting both the risk of postoperative recurrence and molecular typing in breast cancer. This non-invasive approach offers crucial guidance for the diagnosis and treatment of the condition.


Assuntos
Neoplasias da Mama , Recidiva Local de Neoplasia , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/genética , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Medição de Risco/métodos , Valor Preditivo dos Testes , Fatores de Risco , Ultrassonografia/métodos , Idoso , Ultrassonografia Mamária/métodos , Curva ROC
2.
Patient Prefer Adherence ; 18: 1311-1321, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947871

RESUMO

Purpose: To explore 1) the level of shared decision-making (SDM) participation in intraocular lens (IOL) selection in cataract patients and the factors that influence this participation and 2) the relationships between preparation for decision-making (PrepDM)and the level of SDM participation and satisfaction with the decision (SWD). Provide guidance for improving SDM in ophthalmology. Patients and Methods: 176 cataract patients were asked to complete the PrepDM scale, the 9-item Shared Decision Making Questionnaire (SDM-Q-9) and the SWD instrument in IOL decision-making process. Multiple linear regression was used to analyze the influencing factors of the level of SDM. The Process program and bootstrap sampling method was used to test whether the level of participation in SDM was a mediating variable among the three. Results: The SDM-Q-9 median score was 77.78 (IQR 31.11-88.89). Patients with a history of surgery in the operative eye (P=0.022) or PrepDM <60 points (P<0.001) had lower SDM-Q-9 scores than patients with no history of surgery in the operative eye or PrepDM ≥60 points. Patients with an education level lower than primary school had lower SDM-Q-9 scores than patients with other education levels (P<0.05). The PrepDM of cataract patients was positively correlated with the level of SDM (r=0.768, P<0.001) and with the SWD (r=0.727, P<0.001), and the level of SDM was positively correlated with the SWD (r=0.856, P<0.001). The level of SDM fully mediated PrepDM and SDW, with a mediating effect value of 0.128 and a mediating effect of 86.66% of the total effect. Conclusion: The SDM of cataract patients involved in IOL selection was in the upper middle range. Education, history of surgery in the operated eye, and PrepDM were factors that influenced the level of SDM. The level of participation in SDM fully mediated the relationship between PrepDM and SWD.

3.
J Agric Food Chem ; 72(26): 14713-14726, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38885172

RESUMO

Extracellular vesicles released by probiotics have been demonstrated to effectively alleviate intestinal inflammation, yet the precise underlying mechanisms remain unclear. In this research, for the first time, Lactobacillus plantarum UJS001 (LP-UJS) was isolated from fermented sauerkraut in Zhenjiang, China. Thereafter, the therapeutic effect of LP-UJS-derived extracellular vesicles (LP-UJS-EVs) on dextran sulfate sodium-induced ulcerative colitis (UC) in mice was analyzed to elucidate the immune mechanisms. According to our findings, LP-UJS-EVs played a pivotal role in restoring the intestinal barrier and alleviating intestinal inflammation. Notably, LP-UJS-EVs induced M2 polarization of macrophages, promoted the release of IL-10 and TGF-ß, inhibited the release of histamine, IL-6, and TNF-α, and exerted regulatory effects on intestinal microflora, as evidenced by the reduced abundances of Coprococcus, Parabacteroides, Staphylococcus, and Allobaculum, alongside the enhanced abundance of Prevotella. Furthermore, both LP-UJS and LP-UJS-EVs affected the lysine degradation pathway and significantly increased the abundance of related metabolites, especially oxoadipic acid. In summary, our results underscore the substantial therapeutic potential of LP-UJS and its secreted EVs in the treatment of UC.


Assuntos
Colite Ulcerativa , Vesículas Extracelulares , Microbioma Gastrointestinal , Lactobacillus plantarum , Macrófagos , Camundongos Endogâmicos C57BL , Probióticos , Colite Ulcerativa/microbiologia , Colite Ulcerativa/terapia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/imunologia , Lactobacillus plantarum/metabolismo , Animais , Camundongos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/química , Macrófagos/imunologia , Macrófagos/metabolismo , Probióticos/farmacologia , Probióticos/administração & dosagem , Masculino , Humanos , Homeostase , Interleucina-10/metabolismo , Interleucina-10/genética , Interleucina-10/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/genética , Sulfato de Dextrana/efeitos adversos , Fator de Crescimento Transformador beta/metabolismo
4.
Biochem Pharmacol ; 226: 116367, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38876258

RESUMO

Gastric cancer (GC) is a common form of cancer and the leading cause of cancer-related deaths worldwide. Chemotherapy is the primary treatment for patients with unresectable or partially resectable GC. However, its adverse effects and chemoresistance greatly restrict its applicability and efficacy. Although HER2-targeted therapy and immunotherapy have been successfully used for GC treatment, their beneficial population is limited. To expand the range of cancer treatments, drug repurposing has emerged as a promising strategy. In this study, we evaluated the potential of Metformin, an oral anti-hyperglycemic agent, to suppress GC progression both in vivo and in vitro. Functional investigations showed that Metformin significantly inhibits GC proliferation and migration. Furthermore, we discovered that Metformin bound and disrupted STAT1 phosphorylation, inhibiting PRMT1 expression and consequently GC progression. In conclusion, our study not only provides further evidence for the anti-GC role of Metformin but also identifies the direct target mediating the tumor-inhibitory effects of Metformin in GC.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38900242

RESUMO

PURPOSE: Acute myocardial infarction (AMI) is a leading cause of mortality. Neutrophils penetrate injured heart tissue during AMI or ischemia-reperfusion (I/R) injury and produce inflammatory factors, chemokines, and extracellular traps that exacerbate heart injury. Inhibition of the TRAIL-DR5 pathway has been demonstrated to alleviate cardiac ischemia-reperfusion injury in a leukocyte-dependent manner. However, it remains unknown whether TRAIL-DR5 signaling is involved in regulating neutrophil extracellular traps (NETs) release. METHODS: This study used various models to examine the effects of activating the TRAIL-DR5 pathway with soluble mouse TRAIL protein and inhibiting the TRAIL-DR5 signaling pathway using DR5 knockout mice or mDR5-Fc fusion protein on NETs formation and cardiac injury. The models used included a co-culture model involving bone marrow-derived neutrophils and primary cardiomyocytes and a model of myocardial I/R in mice. RESULTS: NETs formation is suppressed by TRAIL-DR5 signaling pathway inhibition, which can lessen cardiac I/R injury. This intervention reduces the release of adhesion molecules and chemokines, resulting in decreased neutrophil infiltration and inhibiting NETs production by downregulating PAD4 in neutrophils. CONCLUSION: This work clarifies how the TRAIL-DR5 signaling pathway regulates the neutrophil response during myocardial I/R damage, thereby providing a scientific basis for therapeutic intervention targeting the TRAIL-DR5 signaling pathway in myocardial infarction.

6.
PeerJ Comput Sci ; 10: e2056, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855222

RESUMO

Mild cognitive impairment (MCI) is a precursor to neurodegenerative diseases such as Alzheimer's disease, and an early diagnosis and intervention can delay its progression. However, the brain MRI images of MCI patients have small changes and blurry shapes. At the same time, MRI contains a large amount of redundant information, which leads to the poor performance of current MCI detection methods based on deep learning. This article proposes an MCI detection method that integrates the attention mechanism and parallel dilated convolution. By introducing an attention mechanism, it highlights the relevant information of the lesion area in the image, suppresses irrelevant areas, eliminates redundant information in MRI images, and improves the ability to mine detailed information. Parallel dilated convolution is used to obtain a larger receptive field without downsampling, thereby enhancing the ability to acquire contextual information and improving the accuracy of small target classification while maintaining detailed information on large-scale feature maps. Experimental results on the public dataset ADNI show that the detection accuracy of the method on MCI reaches 81.63%, which is approximately 6.8% higher than the basic model. The method is expected to be used in clinical practice in the future to provide earlier intervention and treatment for MCI patients, thereby improving their quality of life.

7.
Environ Sci Technol ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934294

RESUMO

Pertechnetate (99TcO4-), a physiologically toxic radioactive anion, is of great concern due to its high mobility in environmental contamination remediation. Although the soluble oxyanion can be photoreduced to sparingly soluble TcO2·nH2O, its effective removal from a strongly acidic aqueous solution remains a challenge. Here, we found that low-crystalline nitrogen-doped titanium oxide (N-TiO2, 0.6 g L-1) could effectively uptake perrhenate (ReO4-, 10 mg L-1, a nonradioactive surrogate for TcO4-) with 50.8% during 360 min under simulated sunlight irradiation at pH 1.0, but P25 and anatase could not. The nitrogen active center formed by trace nitrogen doping in N-TiO2 can promote the separation and transfer of photogenerated carriers. The positive valence band value of N-TiO2 is slightly higher than those of P25 and anatase, which means that the photogenerated holes have a stronger oxidizability. These holes are involved in the formation of strong reducing •CO2- radicals from formic acid oxidation. The active radicals convert ReO4- to Re(VI), which is subsequently disproportionated to Re(IV) and Re(VII). Effective photocatalytic reduction/removal of Re(VII)/Tc(VII) is performed on the material, which may be considered a potential and convenient strategy for technetium decontamination and extraction in a strongly acidic aqueous solution.

8.
Life Sci ; 351: 122790, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38852795

RESUMO

AIMS: Atorvastatin is a commonly used cholesterol-lowering drug that possesses non-canonical anti-inflammatory properties. However, the precise mechanism underlying its anti-inflammatory effects remains unclear. MATERIALS AND METHODS: The acute phase of ulcerative colitis (UC) was induced using a 5 % dextran sulfate sodium (DSS) solution for 7 consecutive days and administrated with atorvastatin (10 mg/kg) from day 3 to day 7. mRNA-seq, histological pathology, and inflammatory response were determined. Intestinal microbiota alteration, tryptophan, and its metabolites were analyzed through 16S rRNA sequencing and untargeted metabolomics. KEY FINDINGS: Atorvastatin relieved the DSS-induced UC in mice, as evidenced by colon length, body weight, disease activity index score and pathological staining. Atorvastatin treatment reduced the level of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Atorvastatin also relieved the intestinal microbiota disorder caused by UC and decreased the proliferation of pernicious microbiota such as Akkermansia and Bacteroides. Atorvastatin dramatically altered tryptophan metabolism and increased the fecal contents of tryptophan, indolelactic acid (ILA), and indole-3-acetic acid (IAA). Furthermore, atorvastatin enhanced the expression level of aryl hydrocarbon receptor (AhR) and interleukin-22 (IL-22) and further promoted the expression level of intestinal tight junction proteins, such as ZO-1 and occludin, in colitis mice. SIGNIFICANCE: These findings indicated that atorvastatin could alleviate UC by regulating intestinal flora disorders, promoting microbial tryptophan metabolism, and repairing the intestinal barrier.


Assuntos
Atorvastatina , Colite Ulcerativa , Sulfato de Dextrana , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Triptofano , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/microbiologia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Atorvastatina/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Triptofano/metabolismo , Camundongos , Masculino , Anti-Inflamatórios/farmacologia , Colo/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Colo/microbiologia
11.
Cont Lens Anterior Eye ; : 102186, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38782621

RESUMO

PURPOSE: Non-adherence to standard wear, care, and follow-up procedures is a major risk factor for contact lens-related complications. The effectiveness of orthokeratology largely depends on the wearer's adherence. However, a deficiency in scales capturing adherence beliefs pertinent to orthokeratology exacerbates the lack of guidance for effective intervention strategies. The purpose of this study is to develop and evaluate the psychometric properties of a new scale based on the Theory of Planned Behavior that assesses the level of adherence among ortho-k wearers. METHODS: This study involved three stages following the STROBE checklist: (1) developing initial scale items based on the Theory of Planned Behavior, a literature review, and a qualitative study; (2) evaluation of content and face validity; (3) psychometric testing on 296 participants. Item analysis, based on Classical Test Theory, assessed the overall consistency, reliability, and validity of the scale. RESULTS: The final 37-item Beliefs about the Orthokeratology Lens Compliance Scale (BOLCS) comprises 11 dimensions. The Cronbach's alpha coefficients for each dimension ranged from 0.560 to 0.798. The folded half reliabilities were 0.845, and the combined reliabilities ranged from 0.676 to 0.793, indicating strong reliability. Item-level CVI (I-CVI) and scale-level CVI/average (S-CVI/Ave) values, assessed by the panel, ranged from 0.71 to 1 and 0.954, respectively. Exploratory and confirmatory factor analyses supported a factor structure consistent with the theoretical model. CONCLUSIONS: The scale's construction adhered to a standardized process, yielding preliminary validation results with satisfactory reliability and validity.

12.
Technol Cancer Res Treat ; 23: 15330338241256814, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38773777

RESUMO

Objective: This prospective study aims to evaluate acute irradiation-induced xerostomia during radiotherapy by utilizing the normalized iodine concentration (NIC) derived from energy spectrum computed tomography (CT) iodine maps. Methods: In this prospective study, we evaluated 28 patients diagnosed with nasopharyngeal carcinoma. At 4 distinct stages of radiotherapy (0, 10, 20, and 30 fractions), each patient underwent CT scans to generate iodine maps. The NIC of both the left and right parotid glands was obtained, with the NIC at the 0-fraction stage serving as the baseline measurement. After statistically comparing the NIC obtained in the arterial phase, early venous phase, late venous phase, and delayed phase, we chose the late venous iodine concentration as the NIC and proceeded to analyze the variations in NIC at each radiotherapy interval. Using the series of NIC values, we conducted hypothesis tests to evaluate the extent of change in NIC within the parotid gland across different stages. Furthermore, we identified the specific time point at which the NIC decay exhibited the most statistically significant results. In addition, we evaluated the xerostomia grades of the patients at these 4 stages, following the radiation therapy oncology group (RTOG) xerostomia evaluation standard, to draw comparisons with the changes observed in NIC. Results: The NIC in the late venous phase exhibited the highest level of statistical significance (P < .001). There was a noticeable attenuation in NIC as the RTOG dry mouth grade increased. Particularly, at the 20 fraction, the NIC experienced the most substantial attenuation (P < .001), a significant negative correlation was observed between the NIC of the left, right, and both parotid glands, and the RTOG evaluation grade of acute irradiation-induced xerostomia (P < .001, r = -0.46; P < .001, r = -0.45; P < .001, r = -0.47). The critical NIC values for the left, right, and both parotid glands when acute xerostomia occurred were 0.175, 0.185, and 0.345 mg/ml, respectively, with AUC = 0.73, AUC = 0.75, and AUC = 0.75. Conclusion: The NIC may be used to evaluate changes in parotid gland function during radiotherapy and acute irradiation-induced xerostomia.


Assuntos
Iodo , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Glândula Parótida , Tomografia Computadorizada por Raios X , Xerostomia , Humanos , Xerostomia/etiologia , Masculino , Glândula Parótida/efeitos da radiação , Feminino , Carcinoma Nasofaríngeo/radioterapia , Pessoa de Meia-Idade , Adulto , Idoso , Neoplasias Nasofaríngeas/radioterapia , Estudos Prospectivos , Lesões por Radiação/etiologia , Lesões por Radiação/diagnóstico , Dosagem Radioterapêutica
13.
Macromol Rapid Commun ; : e2400121, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38636079

RESUMO

The utilization of polymer conformations to construct a variety of superlattices is a common method within the field. However, this technique often results in only long-range ordering rather than the formation of distinct superlattices. In this study, a well-organized array of discrete pancake-shaped superlattices (DPSs) is successfully obtained through the utilization of air-liquid interface self-assembly, facilitated by the confined environment created by a block copolymer. It is crucial to note that both the self-assembly behavior and resulting morphologies of the DPSs can be precisely tuned by adjusting several experimental parameters, most notably the concentration and molecular architecture of the block copolymers. Furthermore, this work provides valuable insights into the formation processes and mechanisms underpinning the DPSs. The approach described here is both straightforward and efficacious, establishing a strong foundation for subsequent research and the development of non-close-packed superlattice structures.

14.
Psychol Res Behav Manag ; 17: 1451-1461, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590759

RESUMO

Background: Diabetes distress (DD) is a negative emotion related to diabetes management and a predictor of depression; it affects diabetic retinopathy (DR) patients' quality of life and disease outcomes. The prevalence of DD was higher in patients undergoing surgery for DR. However, few studies have been conducted on DD in DR surgery patients. The present study aims to investigate the status of DD in DR surgery patients and identify factors associated with DD. Methods: Using a convenience sampling method, 210 DR surgery patients who were admitted to 2 tertiary-level hospitals in Wenzhou City (Zhejiang Province) and Zhengzhou City (Henan Province) from February to June 2023 were selected as research subjects. A questionnaire collecting demographic and disease-related information, the Diabetes Distress Scale, the Summary of Diabetes Self-Management Activities, the Family Care Index Scale, and the Social Support Rating Scale were used to collect data. Statistical analyses included descriptive statistics, t tests, ANOVAs, Pearson's correlation analyses and stepwise multiple linear regression. This study is reported according to the STROBE guidelines. Results: In total, 156 out of 210 (74.29%) DR surgery patients experienced DD, with an average score of 2.13±0.63. The results of the stepwise multiple regression analysis showed that residential location, employment status, self-management level, family support, and social support were significantly associated with DD. These variables accounted for 30.6% of the total variation in DD. Conclusions: DR surgery patients exhibit moderate levels of distress. Health care professionals should pay attention to DD in DR surgery patients and develop targeted interventions to improve the self-management ability of these patients, increase their family support and social support to reduce their DD levels.

15.
J Genet Genomics ; 51(7): 703-713, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38461943

RESUMO

The evolution of light-skin pigmentation among Eurasians is considered as an adaptation to the high-latitude environments. East Asians are ideal populations for studying skin color evolution because of the complex environment of East Asia. Here, we report a strong selection signal for the pigmentation gene phenylalanine hydroxylase (PAH) in light-skinned Han Chinese individuals. The intron mutation rs10778203 in PAH is enriched in East Asians and is significantly associated with skin color of the back of the hand in Han Chinese males (P < 0.05). In vitro luciferase and transcription factor binding assays show that the ancestral allele of rs10778203 could bind to SMAD2 and has a significant enhancer activity for PAH. However, the derived T allele (the major allele in East Asians) of rs10778203 decreases the binding activity of transcription factors and enhancer activity. Meanwhile, the derived T allele of rs10778203 shows a weaker ultraviolet radiation response in A375 cells and zebrafish embryos. Furthermore, rs10778203 decreases melanin production in transgenic zebrafish embryos after ultraviolet B (UVB) treatment. Collectively, PAH is a potential pigmentation gene that regulates skin tanning ability. Natural selection has enriched the adaptive allele, resulting in weakened tanning ability in East Asians, suggesting a unique genetic mechanism for evolutionary skin lightening in East Asians.


Assuntos
Povo Asiático , Pigmentação da Pele , Peixe-Zebra , Pigmentação da Pele/genética , Pigmentação da Pele/efeitos da radiação , Animais , Humanos , Peixe-Zebra/genética , Povo Asiático/genética , Masculino , Fenilalanina Hidroxilase/genética , Fenilalanina Hidroxilase/metabolismo , Melaninas/metabolismo , Melaninas/genética , Alelos , Raios Ultravioleta/efeitos adversos , Seleção Genética , Polimorfismo de Nucleotídeo Único/genética , Evolução Biológica , Animais Geneticamente Modificados/genética , Mutação , População do Leste Asiático
16.
Adv Healthc Mater ; : e2303388, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38537119

RESUMO

Repairing spinal cord injury (SCI) is a global medical challenge lacking effective clinical treatment. Developing human-engineered spinal cord tissues that can replenish lost cells and restore a regenerative microenvironment offers promising potential for SCI therapy. However, creating vascularized human spinal cord-like tissues (VSCT) that mimic the diverse cell types and longitudinal parallel structural features of spinal cord tissues remains a significant hurdle. In the present study, VSCTs are engineered using embryonic human spinal cord-derived neural and endothelial cells on linear-ordered collagen scaffolds (LOCS). Studies have shown that astrocytes and endothelial cells align along the scaffolds in VSCT, supporting axon extension from various human neurons myelinated by oligodendrocytes. After transplantation into SCI rats, VSCT survives at the injury sites and promotes endogenous neural regeneration and vascularization, ultimately reducing scarring and enhancing behavioral functional recovery. It suggests that pre-vascularization of engineered spinal cord tissues is beneficial for SCI treatment and highlights the important role of exogenous endothelial cells in tissue engineering.

17.
Small ; : e2311456, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38497893

RESUMO

Tissue engineering scaffolds can mediate the maneuverability of neural stem cell (NSC) niche to influence NSC behavior, such as cell self-renewal, proliferation, and differentiation direction, showing the promising application in spinal cord injury (SCI) repair. Here, dual-network porous collagen fibers (PCFS) are developed as neurogenesis scaffolds by employing biomimetic plasma ammonia oxidase catalysis and conventional amidation cross-linking. Following optimizing the mechanical parameters of PCFS, the well-matched Young's modulus and physiological dynamic adaptability of PCFS (4.0 wt%) have been identified as a neurogenetic exciter after SCI. Remarkably, porous topographies and curving wall-like protrusions are generated on the surface of PCFS by simple and non-toxic CO2 bubble-water replacement. As expected, PCFS with porous and matched mechanical properties can considerably activate the cadherin receptor of NSCs and induce a series of serine-threonine kinase/yes-associated protein mechanotransduction signal pathways, encouraging cellular orientation, neuron differentiation, and adhesion. In SCI rats, implanted PCFS with matched mechanical properties further integrated into the injured spinal cords, inhibited the inflammatory progression and decreased glial and fibrous scar formation. Wall-like protrusions of PCFS drive multiple neuron subtypes formation and even functional neural circuits, suggesting a viable therapeutic strategy for nerve regeneration and functional recovery after SCI.

18.
Brain Res ; 1833: 148867, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38499234

RESUMO

The rate of early neurological deterioration (END) differs in different subtypes of ischaemic stroke. Previous studies showed PLCL2 gene is a novel susceptibility locus for the occurrence of atherosclerosis and thrombotic events. The objective of this research is to examine the efficacy that PLCL2 may have on the risk of END in large artery atherosclerotic (LAA) stroke. Tagged single nucleotide polymorphisms (SNPs) were identified by a strategy of fine-mapping. The genotyping of the selected SNPs was performed by SNPscan. The impact of PLCL2 on indicating the susceptibility of END in LAA patients was evaluated by binary logistic regression. The SNP-SNP interactions of PLCL2 for END was assessed by generalized multifactor dimensionality reduction (GMDR). A total of 1527 LAA stroke patients were recruited, 582 patients (38 %) experienced END. Compared to participants without END, participants experienced END were much older (P = 0.018), more likely to suffer pre-existing diabetes mellitus (P = 0.036), higher frequent in active tobacco users (P = 0.022) and had much higher median NIHSS on admission (P < 0.001). Rs4685423 was identified to be a predictor to the risk of END: the frequency of END in AA genotype patients is lower than that in AC or CC genotype patients (multivariate-adjusted, OR 0.63; 95 % CI 0.49-0.80; P < 0.001). The SNP-SNP interactions analysis indicates rs4685423 has the greatest impacton the risk of END for LAA patients. The time from admission diagnosis to END onset in AA genotype patients is much later than that in CA or CC genotype patients (log-rank, P = 0.005). In summary, the PLCL2 rs4685423 SNP is probably associated with the END risk in LAA stroke patients.


Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Polimorfismo de Nucleotídeo Único/genética , Idoso , Pessoa de Meia-Idade , Acidente Vascular Cerebral/genética , Predisposição Genética para Doença/genética , Aterosclerose/genética , Cromossomos Humanos Par 3/genética , Fatores de Risco , Genótipo , Arteriosclerose Intracraniana/genética
19.
Proc Natl Acad Sci U S A ; 121(14): e2317574121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38530899

RESUMO

Fine particulate matter (PM2.5) is globally recognized for its adverse implications on human health. Yet, remain limited the individual contribution of particular PM2.5 components to its toxicity, especially considering regional disparities. Moreover, prevention solutions for PM2.5-associated health effects are scarce. In the present study, we comprehensively characterized and compared the primary PM2.5 constituents and their altered metabolites from two locations: Taiyuan and Guangzhou. Analysis of year-long PM2.5 samples revealed 84 major components, encompassing organic carbon, elemental carbon, ions, metals, and organic chemicals. PM2.5 from Taiyuan exhibited higher contamination, associated health risks, dithiothreitol activity, and cytotoxicities than Guangzhou's counterpart. Applying metabolomics, BEAS-2B lung cells exposed to PM2.5 from both cities were screened for significant alterations. A correlation analysis revealed the metabolites altered by PM2.5 and the critical toxic PM2.5 components in both regions. Among the PM2.5-down-regulated metabolites, phosphocholine emerged as a promising intervention for PM2.5 cytotoxicities. Its supplementation effectively attenuated PM2.5-induced energy metabolism disorder and cell death via activating fatty acid oxidation and inhibiting Phospho1 expression. The highlighted toxic chemicals displayed combined toxicities, potentially counteracted by phosphocholine. Our study offered a promising functional metabolite to alleviate PM2.5-induced cellular disorder and provided insights into the geo-based variability in toxic PM2.5 components.


Assuntos
Poluentes Atmosféricos , Doenças Mitocondriais , Humanos , Poluentes Atmosféricos/análise , Fosforilcolina , Material Particulado/análise , Pulmão , Carbono/análise , Monitoramento Ambiental
20.
World J Gastrointest Oncol ; 16(2): 527-542, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38425409

RESUMO

BACKGROUND: An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer (CRC). However, no work is currently available to synthesize the field through bibliometrics. AIM: To analyze the development in the field of "glucose metabolism" (GM), "amino acid metabolism" (AM), "lipid metabolism" (LM), and "nucleotide metabolism" (NM) in CRC by visualization. METHODS: Articles within the abovementioned areas of GM, AM, LM and NM in CRC, which were published from January 1, 1991, to December 31, 2022, are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19. RESULTS: The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields. Meanwhile, China and the United States were two of the most prominent contributors in these four areas. In addition, Gang Wang, Wei Jia, Maria Notarnicola, and Cornelia Ulrich ranked first in publication numbers, while Jing-Yuan Fang, Senji Hirasawa, Wei Jia, and Charles Fuchs were the most cited authors on average in these four fields, respectively. "Gut microbiota" and "epithelial-mesenchymal transition" emerged as the newest burst words in GM, "gut microbiota" was the latest outburst word in AM, "metastasis", "tumor microenvironment", "fatty acid metabolism", and "metabolic reprogramming" were the up-to-date outbreaking words in LM, while "epithelial-mesenchymal transition" and "apoptosis" were the most recently occurring words in NM. CONCLUSION: Research in "cellular metabolism in CRC" is all the rage at the moment, and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC. Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.

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