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1.
Am J Primatol ; : e23627, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613565

RESUMO

Black-and-white snub-nosed monkeys (Rhinopithecus bieti) rely on behavioral and dietary flexibility to survive in temperate latitudes at high-elevation habitats characterized by climate and resource seasonality. However, little is known about how elevation influences their behavioral and dietary flexibility at monthly or seasonal scales. We studied an isolated R. bieti population at Mt. Lasha in the Yunling Provincial Nature Reserve, Yunnan, China, between May 2008 and August 2016 to assess the impacts of elevation on feeding behavior and diet. Across our sample, R. bieti occupied elevations between 3031 and 3637 m above mean sea level (amsl), with a 315.1 m amsl range across months and a 247.3 m amsl range across seasons. Contrary to expectations, individuals spent less time feeding when ranging across higher elevations. Lichen consumption correlated with elevation use across months and seasons, with individuals spending more time feeding on this important resource at higher elevations. Leaf consumption only correlated with elevation use during the spring. Our results suggest that R. bieti do not maximize their food intake at higher elevations and that monthly and seasonal changes in lichen and leaf consumption largely explain variation in elevation use. These findings shed light on the responses of R. bieti to environmental change and offer insight into strategies for conserving their habitats in the face of anthropogenic disturbance.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38607707

RESUMO

Inferring potential drug indications plays a vital role in the drug discovery process. It can be time-consuming and costly to discover novel drug indications through biological experiments. Recently, graph learning-based methods have gained popularity for this task. These methods typically treat the prediction task as a binary classification problem, focusing on modeling associations between drugs and diseases within a graph. However, labeled data for drug indication prediction is often limited and expensive to acquire. Contrastive learning addresses this challenge by aligning similar drug-disease pairs and separating dissimilar pairs in the embedding space. Thus, we developed a model called DrIGCL for drug indication prediction, which utilizes graph convolutional networks and contrastive learning. DrIGCL incorporates drug structure, disease comorbidities, and known drug indications to extract representations of drugs and diseases. By combining contrastive and classification losses, DrIGCL predicts drug indications effectively. In multiple runs of hold-out validation experiments, DrIGCL consistently outperformed existing computational methods for drug indication prediction, particularly in terms of top-k. Furthermore, our ablation study has demonstrated a significant improvement in the predictive capabilities of our model when utilizing contrastive learning. Finally, we validated the practical usefulness of DrIGCL by examining the predicted novel indications of Aspirin. The prediction model's code is available at https://github.com/yuxunluo9/DrIGCL.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38577938

RESUMO

The aim of this study is to evaluate the developments in the treatment and prevalence of hypertension by demographic subgroups in least developed area of China in 2012 and 2022. This population-based cross-sectional study was conducted in 2012 and 2022, we applied stratified multistage random sampling to investigate residents aged 18 years or older in Gansu, the least developed province in the northwest of China. Questionnaires and anthropometric measurements were given to all respondents. The standardized prevalence of hypertension in adults in Gansu increased from 26.1% in 2012 to 28.8% in 2022. Compared with 2012, the control rate remains decreased despite the significantly improved awareness and treatment rates of hypertension in 2022. Apart from the reversal of the control rate, the trend of higher prevalence in men and higher awareness and treatment rates in women has not changed. There was an obviously increase in the proportion of participants who had received health education and hypertension management services from medical workers. The treatment was still primarily monotherapy, and there was no significant improvement in the prescription of medication. The prevalence of hypertension has increased mildly in the least developed region of China over the past decade, and the challenge of hypertension management has shifted from increasing awareness and treatment rates to increasing control rates. The onset and control of hypertension are affected by education methods, BMI, local economic conditions and other factors, and targeted strategies can be adopted to strengthen the management of hypertension in economically underdeveloped areas of China.

4.
Sci Prog ; 107(2): 368504241232537, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567422

RESUMO

Nasopharyngeal carcinoma is a malignant tumor that occurs in the epithelium and mucosal glands of the nasopharynx, and its pathological type is mostly poorly differentiated squamous cell carcinoma. Since the nasopharynx is located deep in the head and neck, early diagnosis and timely treatment are critical to patient survival. However, nasopharyngeal carcinoma tumors are small in size and vary widely in shape, and it is also a challenge for experienced doctors to delineate tumor contours. In addition, due to the special location of nasopharyngeal carcinoma, complex treatments such as radiotherapy or surgical resection are often required, so accurate pathological diagnosis is also very important for the selection of treatment options. However, the current deep learning segmentation model faces the problems of inaccurate segmentation and unstable segmentation process, which are mainly limited by the accuracy of data sets, fuzzy boundaries, and complex lines. In order to solve these two challenges, this article proposes a hybrid model WET-UNet based on the UNet network as a powerful alternative for nasopharyngeal cancer image segmentation. On the one hand, wavelet transform is integrated into UNet to enhance the lesion boundary information by using low-frequency components to adjust the encoder at low frequencies and optimize the subsequent computational process of the Transformer to improve the accuracy and robustness of image segmentation. On the other hand, the attention mechanism retains the most valuable pixels in the image for us, captures the remote dependencies, and enables the network to learn more representative features to improve the recognition ability of the model. Comparative experiments show that our network structure outperforms other models for nasopharyngeal cancer image segmentation, and we demonstrate the effectiveness of adding two modules to help tumor segmentation. The total data set of this article is 5000, and the ratio of training and verification is 8:2. In the experiment, accuracy = 85.2% and precision = 84.9% can show that our proposed model has good performance in nasopharyngeal cancer image segmentation.


Assuntos
Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/diagnóstico por imagem , Carcinoma Nasofaríngeo/diagnóstico por imagem , Epitélio , Pescoço
5.
Artigo em Inglês | MEDLINE | ID: mdl-38569169

RESUMO

With the increasing prevalence of bone tissue diseases, three-dimensional (3D) bioprinting applied to bone tissue engineering for treatment has received a lot of interests in recent years. The research and popularization of 3D bioprinting in bone tissue engineering require bioinks with good performance, which is closely related to ideal material and appropriate construction form. Hydroxyapatite (HAp) is the inorganic component of natural bone and has been widely used in bone tissue engineering and other fields due to its good biological and physicochemical properties. Previous studies have prepared different bioinks containing HAp and evaluated their properties in various aspects. Most bioinks showed significant improvement in terms of rheology and biocompatibility; however, not all of them had sufficiently favorable mechanical properties and antimicrobial activity. The deficiencies in properties of bioink and 3D bioprinting technology limited the applications of bioinks containing HAp in clinical trials. This review article summarizes the construction forms of bioinks containing HAp and its modifications in previous studies, as well as the 3D bioprinting techniques adopted to print bioink containing HAp. In addition, this article summarizes the advantages and underlying mechanisms of bioink containing HAp, as well as its limitations, and suggests possible improvement to facilitate the development of bone tissue engineering bioinks containing HAp in the future.

6.
Med Oncol ; 41(5): 113, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602586

RESUMO

Leukemia is a malignant disease of the hematopoietic system, in which clonal leukemia cells accumulate and inhibit normal hematopoiesis in the bone marrow and other hematopoietic tissues as a result of uncontrolled proliferation and impaired apoptosis, among other mechanisms. In this study, the anti-leukemic effect of a compound (SGP-17-S) extracted from Chloranthus multistachys, a plant with anti-inflammatory, antibacterial and anti-tumor effects, was evaluated. The effect of SGP-17-S on the viability of leukemic cell was demonstrated by MTT assay, cell cycle, and apoptosis were assessed by flow cytometry using PI staining and Annexin V/PI double staining. Combinations of network pharmacology and cellular thermal shift assay (CETSA) with western blot were used to validate agents that act on leukemia targets. The results showed that SGP-17-S inhibited the growth of leukemia cells in a time- and dose-dependent manner. SGP-17-S blocked HEL cells in the G2 phase, induced apoptosis, decreased Bcl-2 and caspase-8 protein expression, and increased Bax and caspase-3 expression. In addition, CETSA revealed that PARP1 is an important target gene for the inhibition of HEL cell growth, and SGP-17-S exerted its action on leukemia cells by targeting PARP1. Therefore, this study might provide new solutions and ideas for the treatment of leukemia.


Assuntos
Leucemia , Humanos , Leucemia/tratamento farmacológico , Ciclo Celular , Proliferação de Células , Divisão Celular , Anexina A5 , Poli(ADP-Ribose) Polimerase-1
7.
Comput Biol Chem ; 110: 108060, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38579550

RESUMO

Developing new drugs is an expensive, time-consuming process that frequently involves safety concerns. By discovering novel uses for previously verified drugs, drug repurposing helps to bypass the time-consuming and costly process of drug development. As the largest family of proteins targeted by verified drugs, G protein-coupled receptors (GPCR) are vital to efficiently repurpose drugs by inferring their associations with drugs. Drug repurposing may be sped up by computational models that predict the strength of novel drug-GPCR pairs interaction. To this end, a number of models have been put forth. In existing methods, however, drug structure, drug-drug interactions, GPCR sequence, and subfamily information couldn't simultaneously be taken into account to detect novel drugs-GPCR relationships. In this study, based on a multi-graph convolutional network, an end-to-end deep model was developed to efficiently and precisely discover latent drug-GPCR relationships by combining data from multi-sources. We demonstrated that our model, based on multi-graph convolutional networks, outperformed rival deep learning techniques as well as non-deep learning models in terms of inferring drug-GPCR relationships. Our results indicated that integrating data from multi-sources can lead to further advancement.

8.
Crit Care ; 28(1): 118, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594772

RESUMO

BACKGROUND: This study aimed to develop an automated method to measure the gray-white matter ratio (GWR) from brain computed tomography (CT) scans of patients with out-of-hospital cardiac arrest (OHCA) and assess its significance in predicting early-stage neurological outcomes. METHODS: Patients with OHCA who underwent brain CT imaging within 12 h of return of spontaneous circulation were enrolled in this retrospective study. The primary outcome endpoint measure was a favorable neurological outcome, defined as cerebral performance category 1 or 2 at hospital discharge. We proposed an automated method comprising image registration, K-means segmentation, segmentation refinement, and GWR calculation to measure the GWR for each CT scan. The K-means segmentation and segmentation refinement was employed to refine the segmentations within regions of interest (ROIs), consequently enhancing GWR calculation accuracy through more precise segmentations. RESULTS: Overall, 443 patients were divided into derivation N=265, 60% and validation N=178, 40% sets, based on age and sex. The ROI Hounsfield unit values derived from the automated method showed a strong correlation with those obtained from the manual method. Regarding outcome prediction, the automated method significantly outperformed the manual method in GWR calculation (AUC 0.79 vs. 0.70) across the entire dataset. The automated method also demonstrated superior performance across sensitivity, specificity, and positive and negative predictive values using the cutoff value determined from the derivation set. Moreover, GWR was an independent predictor of outcomes in logistic regression analysis. Incorporating the GWR with other clinical and resuscitation variables significantly enhanced the performance of prediction models compared to those without the GWR. CONCLUSIONS: Automated measurement of the GWR from non-contrast brain CT images offers valuable insights for predicting neurological outcomes during the early post-cardiac arrest period.


Assuntos
Parada Cardíaca Extra-Hospitalar , Substância Branca , Humanos , Estudos Retrospectivos , Substância Cinzenta/diagnóstico por imagem , Parada Cardíaca Extra-Hospitalar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Prognóstico
9.
Sci Total Environ ; 928: 172453, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38641108

RESUMO

BACKGROUND: Evidence on the association between particulate matter (PM) exposure and prognosis in people living with HIV/AIDS (PWHA) is scarce. We aim to investigate the associations of long-term exposure to PM with AIDS-related deaths and complications. METHODS: We collected follow-up information on 7444 PWHAs from 2000 to 2021 from the HIV/AIDS Comprehensive Response Information Management System of the Wuhan Center for Disease Control and Prevention. The AIDS-related deaths and complications were assessed by physicians every 3 to 6 months, and the monthly average PM concentrations for each PWHA were extracted from the China High Air Pollutants dataset. We employed time-varying Cox regression models to evaluate the associations of the average cumulative PM exposure concentrations with AIDS-related deaths and complications, as well as the mediating effects of AIDS-related complications in PM-induced AIDS-related deaths. RESULTS: For each 1 µg/m3 increase in PM1, PM2.5, and PM10, the adjusted hazard ratios (HRs) for AIDS-related deaths were 1.021 (1.009, 1.033), 1.012 (1.005, 1.020), and 1.010 (1.005, 1.015), respectively; and the HRs for AIDS-related complications were 1.049 (1.034, 1.064), 1.029 (1.020, 1.038), and 1.031 (1.024, 1.037), respectively. AIDS-related complications mediated 18.38 % and 18.68 % of the association of exposure to PM1 and PM2.5 with AIDS-related deaths, respectively. The association of PM exposure with AIDS-related deaths was more significant in older PWHA. Meanwhile, the association between PM exposure and AIDS-related complications was stronger in PWHA with a BMI ≥ 24 kg/m2. CONCLUSION: Long-term exposure to PM is positively associated with AIDS-related deaths and complications, and AIDS-related complications have mediating effects in PM-induced AIDS-related deaths. Our evidence emphasizes that enhanced protection against PM exposure for PWHAs is an additional mitigation strategy to reduce AIDS-related deaths and complications.

10.
Disabil Rehabil ; : 1-15, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38638087

RESUMO

PURPOSE: This review systematically explores and summarise the effects of motor imagery training (MIT) compared to conventional therapy on gait performance in individuals after stroke. MATERIALS AND METHODS: Randomised controlled trials (RCTs) were systematically searched in five electronic databases (PubMed, EMBASE, PsycINFO, OVID Nursing and CINAHL) from inception to 30 December 2022. Studies investigating MITs, targeted at individuals after stroke were eligible. Data were extracted related to study and intervention characteristics. RESULTS: Sixteen studies were included. Compared with 'routine methods of treatment or training', the meta-analyses showed that MIT was more effective in improving cadence immediately post intervention (SMD: 1.22, 95% CI: 0.59, 1.85, p = 0.0001, I2 = 25%) and at 1- or 2-months post intervention (SMD: 0.78, 95% CI: 0.35, 1.20, p = 0.0004, I2 = 46%). The results also showed that MIT improves the step length of the affected side and the unaffected side at 1- or 2-months post intervention. Separate meta-analyses were also conducted on different tests of walking endurance (assessed by the 6-Minute Walk Test) and functional mobility (assessed by the Timed-Up-and-Go test). CONCLUSIONS: MIT effectively improved gait performance. The findings in individuals after stroke remain inconclusive due to significant heterogeneity in included studies.


Restoring gait performance and daily functional abilities is an important goal of post-stroke rehabilitation.Motor imagery training (MIT) may be a promising method to improve gait restoration and is expected to provide another option for the effective rehabilitation of stroke patients.This review highlights the limited research on MIT and thus the limited evidence to guide clinical rehabilitation.In the stroke rehabilitation, clinical specialists may consider incorporating MIT into the treatment programme to improve patients' gait performance and ensure effective early lower limb rehabilitation.

11.
Materials (Basel) ; 17(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612062

RESUMO

The effect of hydrogen content on the deformation and fracture behavior of 27Cr-4Mo-2Ni super ferritic stainless steel (SFSS) was investigated in this study. It was shown that the plasticity and yield strength of SFSS were very susceptible to hydrogen content. The introduction of hydrogen led to a significant decrease in elongation and a concurrent increase in yield strength. Nevertheless, a critical threshold was identified in the elongation reduction, after which the elongation remained approximately constant even with more hydrogen introduced, while the yield strength exhibited a monotonic increase with increasing hydrogen content within the experimental range, attributed to the pinning effect of the hydrogen Cottrell atmosphere on dislocations. Furthermore, the hydrogen-charged SFSS shows an apparent drop in flow stress after upper yielding and a reduced work hardening rate during the subsequent plastic deformation. The more hydrogen is charged, the more the flow stress drops, and the lower the work hardening rate becomes.

12.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1327-1334, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621980

RESUMO

This study aims to investigate whether baicalin induces ferroptosis in HepG2 cells and decipher the underlying mechanisms based on network pharmacology and cell experiments. HepG2 cells were cultured in vitro and the cell viability was detected by the cell counting kit-8(CCK-8). The transcriptome data of hepatocellular carcinoma were obtained from the Cancer Genome Atlas(TCGA), and the ferroptosis gene data from FerrDb V2. The DEG2 package was used to screen the differentially expressed genes(DEGs), and the common genes between DEGs and ferroptosis genes were selected as the target genes that mediate ferroptosis to regulate hepatocellular carcinoma progression. The functions and structures of the target genes were analyzed by Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment with the thresholds of P<0.05 and |log_2(fold change)|>0.5. DCFH-DA probe was used to detect the changes in the levels of cellular reactive oxygen species(ROS) in each group. The reduced glutathione(GSH) assay kit was used to measure the cellular GSH level, and Fe~(2+) assay kit to determine the Fe~(2+) level. Real-time quantitative PCR(RT-PCR) was employed to measure the mRNA levels of glutathione peroxidase 4(GPX4) and solute carrier family 7 member 11(SLC7A11) in each group. Western blot was employed to determine the protein levels of GPX4, SLC7A11, phosphatidylinositol 3-kinase(PI3K), p-PI3K, protein kinase B(Akt), p-Akt, forkhead box protein O3a(FoxO3a), and p-FoxO3a in each group. The results showed that treatment with 200 µmol·L~(-1) baicalin for 48 h significantly inhibited the viability of HepG2 cells. Ferroptosis in hepatocellular carcinoma could be regulated via the PI3K/Akt signaling pathway. The cell experiments showed that baicalin down-regulated the expression of SLC7A11 and GPX4, lowered the GSH level, and increased ROS accumulation and Fe~(2+) production in HepG2 cells. However, ferrostatin-1, an ferroptosis inhibitor, reduced baicalin-induced ROS accumulation, up-regulated the expression of SLC7A11 and GPX4, elevated the GSH level, and decreased PI3K, Akt, and FoxO3a phosphorylation. In summary, baicalin can induce ferroptosis in HepG2 cells by inhibiting the ROS-mediated PI3K/Akt/FoxO3a pathway.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Flavonoides , Neoplasias Hepáticas , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Fosfatidilinositol 3-Quinases/genética , Espécies Reativas de Oxigênio , Células Hep G2 , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Transdução de Sinais
13.
Geriatr Nurs ; 57: 140-146, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38643734

RESUMO

OBJECTIVES: To investigate the utilization of mobility device, whether age and gender-related use disparities exist, and whether falls can further explain use disparities over time among Chinese older adults in need of devices. METHODS: Community-dwelling older adults who needed mobility devices and completed four waves of the China Health and Retirement Survey 2011-2018 were included (N = 1,302). A categorical variable was created to represent respondents' intersectionality of age (50-64, 65-74, and ≥75 years) and gender (men vs. women). RESULTS: The baseline prevalence of device use was 18.2 % (n = 237). Overall, the device use increased over time. Intersectionality-wise, oldest-old women were 1.53 times more likely than youngest-old men to use devices over time. Respondents with falls were more likely to use devices over time. CONCLUSIONS: Older adults with mobility impairment, especially the oldest-old women and those with falls, lag in mobility devices utilization, suggesting future tailored interventions to support these populations.

14.
Obes Rev ; : e13738, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491337

RESUMO

Mounting evidence shows that bisphenol A (BPA) is associated with metabolic risk factors. The aim of this study was to review related epidemiologic studies and conduct a meta-analysis to quantitatively estimate the association between BPA and metabolic syndrome. Four electronic databases were systematically searched to identify suitable articles. A total of 47 published studies were finally included. Two studies involved metabolic syndrome. Of the 17, 17, 14, and 13 studies on the relationship between BPA with abdominal obesity, blood pressure, fasting plasma glucose, and dyslipidemia, 10, 6, 3, and 4 studies were included in the meta-analysis, respectively. The results showed that the risk of abdominal obesity increased with the increase of BPA exposure, especially in the group with higher BPA exposure levels (Quartile 2 vs. Quartile 1, pooled OR = 1.16, 95%CI: 1.01, 1.33; Q3 vs. Q1 , pooled OR = 1.31, 95%CI: 1.13, 1.51; Q4 vs. Q1 , pooled OR = 1.40, 95%CI: 1.21, 1.61). However, there was no significant correlation between BPA exposure and metabolic syndrome components including hypertension, abnormal fasting plasma glucose, and dyslipidemia. The present study found that BPA exposure is significantly associated with a higher risk of abdominal obesity. However, the relationship between BPA with metabolic syndrome and its other components needs further longitudinal studies to verify.

15.
Viruses ; 16(3)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38543836

RESUMO

Enterovirus infection and enterovirus infection with severe complications (EVSC) are critical issues in several aspects. However, there is no suitable predictive tool for these infections. A climate factor complex (CFC) containing several climate factors could provide more effective predictions. The ping-year factor (PYF) and El Niño-Southern Oscillation (ENSO) are possible CFCs. This study aimed to determine the relationship between these two CFCs and the incidence of enterovirus infection. Children aged 15 years and younger with enterovirus infection and/or EVSC were enrolled between 2007 and 2022. Each year was categorized into a ping-year or non-ping-year according to the PYF. Poisson regression was used to evaluate the associations between the PYF, ENSO, and the incidence of enterovirus infection. Compared to the ping-year group, the incidence rate of enterovirus infection, the incidence rate of EVSC, and the ratio of EVSC in the non-ping-year group were 1.24, 3.38, and 2.73 times higher, respectively (p < 0.001). For every one-unit increase in La Niña, the incidence rate of enterovirus infection decreased to 0.96 times (p < 0.001). Our study indicated that CFCs could be potential predictors for enterovirus infection, and the PYF was more suitable than ENSO. Further research is needed to improve the predictive model.


Assuntos
El Niño Oscilação Sul , Infecções por Enterovirus , Criança , Humanos , Taiwan/epidemiologia , Mudança Climática , Incidência , Infecções por Enterovirus/epidemiologia
16.
Zool Res ; 45(2): 284-291, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38485498

RESUMO

Hereditary hearing loss (HHL), a genetic disorder that impairs auditory function, significantly affects quality of life and incurs substantial economic losses for society. To investigate the underlying causes of HHL and evaluate therapeutic outcomes, appropriate animal models are necessary. Pigs have been extensively used as valuable large animal models in biomedical research. In this review, we highlight the advantages of pig models in terms of ear anatomy, inner ear morphology, and electrophysiological characteristics, as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss. Additionally, we discuss the prospects, challenges, and recommendations regarding the use pig models in HHL research. Overall, this review provides insights and perspectives for future studies on HHL using porcine models.


Assuntos
Orelha Interna , Perda Auditiva Neurossensorial , Perda Auditiva , Doenças dos Suínos , Animais , Suínos/genética , Qualidade de Vida , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/veterinária , Perda Auditiva/genética , Perda Auditiva/terapia , Perda Auditiva/veterinária , Modelos Animais
17.
Biomaterials ; 307: 122529, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38489911

RESUMO

Muscle tissue engineering is a promising therapeutic strategy for volumetric muscle loss (VML). Among them, decellularized extracellular matrix (dECM) biological scaffolds have shown certain effects in restoring muscle function. However, researchers have inconsistent or even contradictory results on whether dECM biological scaffolds can efficiently regenerate muscle fibers and restore muscle function. This suggests that therapeutic strategies based on dECM biological scaffolds need to be further optimized and developed. In this study, we used a recellularization method of perfusing adipose-derived stem cells (ASCs) and L6 into adipose dECM (adECM) through vascular pedicles. On one hand, this strategy ensures sufficient quantity and uniform distribution of seeded cells inside scaffold. On the other hand, auxiliary L6 cells addresses the issue of low myogenic differentiation efficiency of ASCs. Subsequently, the treatment of VML animal experiments showed that the combined recellularization strategy can improve muscle regeneration and angiogenesis than the single ASCs recellularization strategy, and the TA of former had greater muscle contraction strength. Further single-nucleus RNA sequencing (snRNA-seq) analysis found that L6 cells induced ASCs transform into a new subpopulation of cells highly expressing Mki67, CD34 and CDK1 genes, which had stronger ability of oriented myogenic differentiation. This study demonstrates that co-seeding ASCs and L6 cells through vascular pedicles is a promising recellularization strategy for adECM biological scaffolds, and the engineered muscle tissue constructed based on this has significant therapeutic effects on VML. Overall, this study provides a new paradigm for optimizing and developing dECM-based therapeutic strategies.


Assuntos
Matriz Extracelular Descelularizada , Doenças Musculares , Animais , Matriz Extracelular , Regeneração , Engenharia Tecidual/métodos , Células-Tronco , Obesidade , Músculo Esquelético/fisiologia , Tecidos Suporte
18.
Mol Immunol ; 169: 66-77, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38503139

RESUMO

Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown etiology. It is marked by the production of pathogenic autoantibodies and the deposition of immune complexes. Lupus nephritis (LN) is a prevalent and challenging clinical complications of SLE. Cortex Moutan contains paeonol as its main effective component. In this study, using the animal model of SLE induced by R848, it was found that paeonol could alleviate the lupus-like symptoms of lupus mouse model induced by R848 activating TLR7, reduce the mortality and ameliorate the renal damage of mice. In order to explore the mechanism of paeonol on lupus nephritis, we studied the effect of paeonol on the polarization of Raw264.7 macrophages in vitro. The experimental results show that paeonol can inhibit the polarization of macrophages to M1 and promote their polarization to M2, which may be related to the inhibition of MAPK and NF-κB signaling pathways. Our research provides a new insight into paeonol in the treatment of lupus nephritis, which is of great importance for the treatment of systemic lupus erythematosus and its complications.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Camundongos , Animais , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/metabolismo , Acetofenonas/farmacologia , Acetofenonas/metabolismo , Macrófagos/metabolismo
19.
Phytomedicine ; 128: 155521, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38489891

RESUMO

BACKGROUND: The ancient Chinese herb Salvia miltiorrhiza Bunge (Danshen), plays the important role in cardiovascular and cerebrovascular disease. Furthermore, Danshen could also be used for curing carcinogenesis. Up to now, the anti-tumor effects of the main active constituents of Danshen have made great progress. However, the bioavailability of the active constituents of Danshen were restricted by their unique physical characteristics, like low oral bioavailability, rapid degradation in vivo and so on. PURPOSE: With the leap development of nano-delivery systems, the shortcomings of the active constituents of Danshen have been greatly ameliorated. This review tried to summarize the recent progress of the active constituents of Danshen based delivery systems used for anti-tumor therapeutics. METHODS: A systematic literature search was conducted using 5 databases (Embase, Google scholar, PubMed, Scopus and Web of Science databases) for the identification of relevant data published before September 2023. The words "Danshen", "Salvia miltiorrhiza", "Tanshinone", "Salvianolic acid", "Rosmarinic acid", "tumor", "delivery", "nanomedicine" and other active ingredients contained in Danshen were searched in the above databases to gather information about pharmaceutical decoration for the active constituents of Danshen used for anti-tumor therapeutics. RESULTS: The main extracts of Danshen could inhibit the proliferation of tumor cells effectively and a great deal of studies were conducted to design drug delivery systems to ameliorate the anti-tumor effect of the active contents of Danshen through different ways, like improving bioavailability, increasing tumor targeting ability, enhancing biological barrier permeability and co-delivering with other active agents. CONCLUSION: This review systematically represented recent progress of pharmaceutical decorations for the active constituents of Danshen used for anti-tumor therapeutics, revealing the diversity of nano-decoration skills and trying to inspire more designs of Danshen based nanodelivery systems, with the hope that bringing the nanomedicine of the active constituents of Danshen for anti-tumor therapeutics from bench to bedside in the near future.

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