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1.
J Chin Med Assoc ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860774

RESUMO

BACKGROUND: Drug addiction is a social and medical problem that must be urgently addressed. The nucleus accumbens (NAc) is closely related to addiction-related learning memory, and γ-aminobutyric acid type B receptor (GABABR) is a potential target for the treatment of drug addiction. However, the role of GABABR activity levels in the NAc in cocaine addiction is unclear. METHODS: In this study, we established an animal model of cocaine dependence, modulated the level of GABABR activity, applied a conditioned place preference assay (CPP) to assess the role of the NAc in reconsolidation of addiction memory, evaluated learning and memory functions by behavioral experiments, examined the expression of GB1, GB2, CREB, p-CREB, PKA, ERK, and BDNF in the NAc by molecular biology experiments, and screened differentially significantly expressed genes by transcriptome sequencing. RESULTS: Our study showed that the GABAB receptor agonist BLF had a significant effect on locomotor distance in rats, promoted an increase in GABA levels and significantly inhibited the PKA and ERK1/2/CREB/BDNF signaling pathways. Moreover, transcriptome sequencing showed that GABABR antagonist intervention identified a total of 21 upregulated mRNAs and 21 downregulated mRNAs. The DE mRNA genes were mainly enriched in tyrosine metabolism; however, further study is needed. CONCLUSION: GABABR activity in the NAc is involved in the regulation of cocaine addiction and may play an important role through key mRNA pathways.

2.
Asian J Androl ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38856299

RESUMO

ABSTRACT: Male infertility is a global issue caused by poor sperm quality, particularly motility. Enhancement of the sperm quality may improve the fertilization rate in assisted reproductive technology (ART) treatment. Scriptaid, with a novel human sperm motility-stimulating activity, has been investigated as a prospective agent for improving sperm quality and fertilization rate in ART. We evaluated the effects of Scriptaid on asthenozoospermic (AZS) semen, including its impact on motility stimulation and protective effects on cryopreservation and duration of motility, by computer-aided sperm analysis (CASA). Sperm quality improvement by Scriptaid was characterized by increased hyaluronan-binding activity, tyrosine phosphorylation, adenosine triphosphate (ATP) concentration, mitochondrial membrane potential, and an ameliorated AZS fertilization rate in clinical intracytoplasmic sperm injection (ICSI) experiments. Furthermore, our identification of active Scriptaid analogs and different metabolites induced by Scriptaid in spermatozoa lays a solid foundation for the future biomechanical exploration of sperm function. In summary, Scriptaid is a potential candidate for the treatment of male infertility in vitro as it improves sperm quality, prolongs sperm viability, and increases the fertilization rate.

3.
Int J Med Robot ; 20(3): e2649, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38847242

RESUMO

BACKGROUND: Endoscope retrograde cholangiopancreatography is a standard surgical treatment for gallbladder and pancreatic diseases. However, surgeons is at high risk and require sufficient surgical experience and skills. METHODS: (1) The simultaneous localisation and mapping technique to reconstruct the surgical environment. (2) The preoperative 3D model is transformed into the intraoperative video environment to implement the multi-modal fusion. (3) A framework for virtual-to-real projection based on hand-eye alignment. For the purpose of projecting the 3D model onto the imaging plane of the camera, it uses position data from electromagnetic sensors. RESULTS: Our AR-assisted navigation system can accurately guide physicians, which means a distance of registration error to be restricted to under 5 mm and a projection error of 5.76 ± 2.13, and the intubation procedure is done at 30 frames per second. CONCLUSIONS: Coupled with clinical validation and user studies, both the quantitative and qualitative results indicate that our navigation system has the potential to be highly useful in clinical practice.


Assuntos
Realidade Aumentada , Colangiopancreatografia Retrógrada Endoscópica , Imagens de Fantasmas , Cirurgia Assistida por Computador , Humanos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Cirurgia Assistida por Computador/métodos , Cirurgia Assistida por Computador/instrumentação , Imageamento Tridimensional/métodos , Sistemas de Navegação Cirúrgica , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/instrumentação , Reprodutibilidade dos Testes
4.
Front Oncol ; 14: 1325362, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854734

RESUMO

Introduction: Magnetic resonance imaging (MRI)-guided wire localization can be applied to assist to remove suspected breast lesions accurately. This study aimed to evaluate the clinical application value of this technique in Chinese women. Methods: A total of 126 patients (131 lesions) who had underwent such technique in our hospital from April 2017 to June 2023 were enrolled. 1.5T MRI system and a wire localization device were used. Image characteristics, clinical features and postoperative pathology were collected and analyzed. Results: All of 126 patients (131 lesions) were successfully localized by MRI and excised for biopsy. There were 39 malignant lesions (29.77%) and 92 benign lesions (70.23%). There was no significant correlation between the morphology of DCE-MRI and the ratio of malignant lesions (P=0.763), while there was a statistical correlation between the BPE, TIC curve and the malignancy rate (P<0.05). All the lesions were assessed according to BI-RADS category of MRI (C4A=77, C4B=40, C4C=12, C5=2). The malignancy rates were as follows: 16.88% for 4A lesions (13/77), 37.50% for 4B lesions (15/40), 75.00% for 4C lesions (9/12) and 100% for 5 lesions (2/2). There was a significant correlation between the BI-RADS category and the incidence of benign-to-malignant lesions (P<0.001). Conclusion: MRI-guided wire localization can assist to remove suspected breast lesions early, safely and accurately. This technique makes up for the deficiency of X-ray and ultrasound, improves the accuracy of diagnosis and resection therapy in intraductal carcinoma and early invasive carcinoma, and helps to improve the the prognosis of breast cancer.

5.
iScience ; 27(6): 110029, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38883844

RESUMO

Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), unfortunately encounters resistance in most patients, leading to disease progression. Traditional approaches to counteract this resistance, particularly those targeting the RAF-MEK-ERK pathway, often face clinical feasibility limitations. Magnetic hyperthermia (MH), unlike conventional thermal therapies, emerges as a promising alternative. It uniquely combines magnetothermal effects with an increase in reactive oxygen species (ROS). This study found the potential of intracellular MH enhanced the efficacy of sorafenib, increased cellular sensitivity to sorafenib, and reversed sorafenib resistance by inhibiting the RAF-MEK-ERK pathway in an ROS-dependent manner in a sorafenib-resistant HCC cell. Further, in a sorafenib-resistant HCC mouse model, MH significantly sensitized tumors to sorafenib therapy, resulting in inhibited tumor growth and improved survival rates. This presents a promising strategy to overcome sorafenib resistance in HCC, potentially enhancing therapeutic outcomes for patients with this challenging condition.

6.
Comput Biol Med ; 178: 108754, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38878404

RESUMO

BACKGROUND: Lumbar disc herniation (LDH) is a prevalent spinal disease that can result in severe pain, with Magnetic resonance imaging (MRI) serving as a commonly diagnostic tool. However, annotating numerous MRI images, necessary for deep learning based LDH diagnosis, can be challenging and labor-intensive. Semi-supervised learning, mainly utilizing pseudo labeling and consistency regularization, can leverage limited labeled images and abundant unlabeled images. However, consistency regularization solely focuses on maintaining the semantic consistency of transformed unlabeled data but fails to utilize the semantic information from labeled data to guide the unlabeled data, and additionally, pseudo labeling is prone to confirmation bias. METHOD: We propose SeCoFixMatch, an innovative approach that seamlessly integrates semantic contrast and uncertainty-aware pseudo labeling into semi-supervised learning. Semantic contrast constraints the semantic consistency between labeled and unlabeled images. Pseudo labels are generated by combining predictive confidence and uncertainty, with uncertainty computing by optimizing the Kullback-Leibler (KL) loss between predictive and target Dirichlet distribution. RESULTS: Comparison with other semi-supervised models and ablation experiment with varying labeled data demonstrate the effectiveness and generalization of proposed model. Notably, SeCoFixMatch, trained with just 40 labels, outperforms the baseline model trained with 200 labels, reducing the annotation effort by a remarkable 80%. CONCLUSIONS: Proposed pseudo labeling algorithm generates more precise pseudo labels for semantic contrastive learning and semantic contrastive learning facilitates better feature representation, thereby further improving the prediction accuracy of pseudo label. The mutual reinforcement of pseudo labeling and semantic contrast constraints boosts the performance of semi-supervised algorithm.

7.
Medicine (Baltimore) ; 103(24): e38162, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38875384

RESUMO

This study employs CiteSpace software to analyze the research status, hotspots, and trends of primary Sjogren syndrome (pSS). Relevant publications from 1999 to 2023 were searched in the Web of Science Core Collection (WoSCC) set, followed by generating a network map using CiteSpace software to identify top authors, institutions, countries, keywords, journals, references, and research trends. A total of 3564 valid articles were included in this study. The People Republic of China had the highest number of articles (n = 524), while the University of Bergen emerged as the institution with the highest publication count (n = 94). Mariette X was identified as the author with the most publications (n = 67), whereas Vitali C received recognition as the most cited author (n = 1706). Annals of Rheumatic Diseases stood out as the journal with the highest citation count (n = 2530). Notably, an article published in the Annals of Rheumatic Diseases in 2017 garnered significant attention by being cited a remarkable 304 times. The bibliometric analysis reveals that key areas of research in pSS encompass investigating pathogenesis; advancing and applying targeted biological agents; and establishing treatment and diagnostic standards.


Assuntos
Bibliometria , Síndrome de Sjogren , Humanos , Software
8.
Front Med (Lausanne) ; 11: 1383252, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835792

RESUMO

Objective: To investigate the clinical characteristics and risk factors of patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. Methods: A retrospective analysis of general clinical data was conducted on patients with SARS-CoV-2 omicron infection complicated with hypertension, coronary heart disease, and heart failure admitted to one hospital in Guangdong Province from December 1, 2022, to February 28, 2023. Clinical symptoms, laboratory tests, imaging examinations, treatment, and clinical outcomes were collected. Multivariate logistic regression analysis was used to analyze the risk factors for mortality in patients with SARS-CoV-2 Omicron variant infection complicated with cardiovascular diseases. ROC curves were drawn to evaluate the predictive value of CRP, D-dimer, and CK-MB in predicting the risk of death. Results: A total of 364 confirmed cases were included, divided into the asymptomatic group, mild to moderate group, and severe to critically ill group based on the symptoms of COVID-19. There were 216 males (59.34%) and 148 females (40.66%), with a median age of 75 years. The differences between the three groups in terms of sex and age were statistically significant (p < 0.05). The top three underlying diseases were hypertension (288 cases, 79.12%), coronary heart disease (100 cases, 27.47%), and diabetes (84 cases, 23.08%). The differences in unvaccinated and triple-vaccinated patients among the three groups were statistically significant (p < 0.05). The common respiratory symptoms were cough in 237 cases (65.11%) and sputum production in 199 cases (54.67%). In terms of laboratory tests, there were statistically significant differences in neutrophils, lymphocytes, red blood cells, C-reactive protein, D-dimer, aspartate aminotransferase, and creatinine among the three groups (p < 0.05). In imaging examinations, there were statistically significant differences among the three groups in terms of unilateral pulmonary inflammation, bilateral pulmonary inflammation, and bilateral pleural effusion (p < 0.05). There were statistically significant differences among the three groups in terms of antibiotic treatment, steroid treatment, oxygen therapy, nasal cannula oxygen inhalation therapy, non-invasive ventilation, and tracheal intubation ventilation (p < 0.05). Regarding clinical outcomes, there were statistically significant differences among the three groups in terms of mortality (p < 0.05). Multivariate logistic regression analysis showed that CRP (OR = 1.012, 95% CI = 1.004-1.019) and D-dimer (OR = 1.117, 95% CI = 1.021-1.224) were independent risk factors for patient mortality. The predictive value of CRP, D-dimer, and CK-MB for the risk of death was assessed. D-dimer had the highest sensitivity (95.8%) in predicting patient mortality risk, while CRP had the highest specificity (84.4%). Conclusion: For patients with COVID-19 and concomitant cardiovascular diseases without contraindications, early administration of COVID-19 vaccines and booster shots can effectively reduce the mortality rate of severe cases. Monitoring biomarkers such as CRP, D-dimer, and CK-MB and promptly providing appropriate care can help mitigate the risk of mortality in patients.

9.
Front Endocrinol (Lausanne) ; 15: 1407503, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38836234

RESUMO

Background: Type 2 diabetes mellitus (T2DM) and hearing loss (HL) constitute significant public health challenges worldwide. Recently, the association between T2DM and HL has aroused attention. However, possible residual confounding factors and other biases inherent to observational study designs make this association undetermined. In this study, we performed univariate and multivariable Mendelian Randomization (MR) analysis to elucidate the causal association between T2DM and common hearing disorders that lead to HL. Methods: Our study employed univariate and multivariable MR analyses, with the Inverse Variance Weighted method as the primary approach to assessing the potential causal association between T2DM and hearing disorders. We selected 164 and 9 genetic variants representing T2DM from the NHGRI-EBI and DIAGRAM consortium, respectively. Summary-level data for 10 hearing disorders were obtained from over 500,000 participants in the FinnGen consortium and MRC-IEU. Sensitivity analysis revealed no significant heterogeneity of instrumental variables or pleiotropy was detected. Results: In univariate MR analysis, genetically predicted T2DM from both sources was associated with an increased risk of acute suppurative otitis media (ASOM) (In NHGRI-EBI: OR = 1.07, 95% CI: 1.02-1.13, P = 0.012; In DIAGRAM: OR = 1.14, 95% CI: 1.02-1.26, P = 0.016). Multivariable MR analysis, adjusting for genetically predicted sleep duration, alcohol consumption, body mass index, and smoking, either individually or collectively, maintained these associations. Sensitivity analyses confirmed the robustness of the results. Conclusion: T2DM was associated with an increased risk of ASOM. Strict glycemic control is essential for the minimization of the effects of T2DM on ASOM.


Assuntos
Diabetes Mellitus Tipo 2 , Análise da Randomização Mendeliana , Otite Média Supurativa , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Otite Média Supurativa/genética , Otite Média Supurativa/complicações , Otite Média Supurativa/epidemiologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Doença Aguda , Perda Auditiva/genética , Perda Auditiva/epidemiologia , Perda Auditiva/etiologia , Feminino , Masculino , Predisposição Genética para Doença
10.
Quant Imaging Med Surg ; 14(6): 4155-4176, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38846275

RESUMO

Background: Dual-energy computed tomography (DECT) is a promising technique, which can provide unique capability for material quantification. The iterative reconstruction of material maps requires spectral information and its accuracy is affected by spectral mismatch. Simultaneously estimating the spectra and reconstructing material maps avoids extra workload on spectrum estimation and the negative impact of spectral mismatch. However, existing methods are not satisfactory in image detail preservation, edge retention, and convergence rate. The purpose of this paper was to mine the similarity between the reconstructed images and the material images to improve the imaging quality, and to design an effective iteration strategy to improve the convergence efficiency. Methods: The material-image subspace decomposition-based iterative reconstruction (MISD-IR) with spectrum estimation was proposed for DECT. MISD-IR is an optimized model combining spectral estimation and material reconstruction with fast convergence speed and promising noise suppression capability. We proposed to reconstruct the material maps based on extended simultaneous algebraic reconstruction techniques and estimation of the spectrum with model spectral. To stabilize the iteration and alleviate the influence of errors, we introduced a weighted proximal operator based on the block coordinate descending algorithm (WP-BCD). Furthermore, the reconstructed computed tomography (CT) images were introduced to suppress the noise based on subspace decomposition, which relies on non-local regularization to prevent noise accumulation. Results: In numerical experiments, the results of MISD-IR were closer to the ground truth compared with other methods. In real scanning data experiments, the results of MISD-IR showed sharper edges and details. Compared with other one-step iterative methods in the experiment, the running time of MISD-IR was reduced by 75%. Conclusions: The proposed MISD-IR can achieve accurate material decomposition (MD) without known energy spectrum in advance, and has good retention of image edges and details. Compared with other one-step iterative methods, it has high convergence efficiency.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38889009

RESUMO

Photoreduction of CO2 with water into chemical feedstocks of fuels provides a green way to help solve both the energy crisis and carbon emission issues. Metal-organic frameworks (MOFs) show great potential for CO2 photoreduction. However, poor water stability and sluggish charge transfer could limit their application. Herein, three water-stable MOFs functionalized with electron-donating methyl groups and/or electron-withdrawing trifluoromethyl groups are obtained for the CO2 photoreduction. Compared with UiO-67-o-CF3-CH3 and UiO-67-o-(CF3)2, UiO-67-o-(CH3)2 achieves excellent performance with an average CO generation rate of 178.0 µmol g-1 h-1 without using any organic solvent or sacrificial reagent. The superior photocatalytic activity of UiO-67-o-(CH3)2 is attributed to the fact that compared with trifluoromethyl groups, methyl groups could not only elevate CO2 adsorption capacity and reduction potential but also promote photoinduced charge separation and migration. These are evidenced by gas physisorption, photoluminescence, time-resolved photoluminescence, electrochemical impedance spectroscopy, transient photocurrent characteristics, and density functional theory calculations. The possible working mechanisms of electron-donating methyl groups are also proposed. Moreover, UiO-67-o-(CH3)2 demonstrates excellent reusability for the CO2 reduction. Based on these results, it could be affirmed that the strategy of modulating substituent electronegativity could provide guidance for designing highly efficient photocatalysts.

12.
Huan Jing Ke Xue ; 45(6): 3638-3648, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38897783

RESUMO

To achieve efficient resource utilization of fly ash and multi-source organic waste, a composting experiment was carried out to investigate the effects of fly ash on co-aerobic composting using kitchens, chicken manure, and sawdust (15:5:2). The effects of different application doses (5 % and 10 %, calculated in total wet weight of organic solid waste) of fly ash on physical and chemical properties, nutrient elements, and bacterial community structure during co-composting were evaluated. The results showed that the addition dose of 5 % and 10 % fly ash significantly increased the highest temperature (56.6 ℃ and 56.9 ℃) and extended the thermophilic period to nine days. Compared with that in the control, the total nutrient content of compost products in the treatments of 5 % FA and 10 % FA was increased by 4.09 % and 13.55 %, respectively. The bacterial community structure changed greatly throughout the composting, and the bacterial diversity of all treatments increased obviously. In the initial stage of composting, Proteobacteria was the dominant phylum of bacteria, with a relative abundance ranging from 35.26 % to 39.40 %. In the thermophilic period, Firmicutes dominated; its relative abundance peaked at 52.46 % in the 5 % FA treatment and 67.72 % in the 10 % FA treatment. Bacillus and Thermobifida were the predominant groups in the thermophilic period of composting. The relative abundance of Bacillus and Thermobifida in the 5 % FA and 10 % FA treatments were 33.41 % and 62.89 %(Bacillus) and 33.06 % and 12.23 %(Thermobifida), respectively. The results of the redundancy analysis (RDA) revealed that different physicochemical indicators had varying degrees of influence on bacteria, with organic matter, pH, available phosphorus, and available potassium being the main environmental factors influencing bacterial community structure. In summary, the addition of fly ash promoted the harmlessness and maturation of co- aerobic composting of urban multi-source organic waste, while optimizing microbial community structure and improving the quality and efficiency of composting.


Assuntos
Bactérias , Cidades , Cinza de Carvão , Compostagem , Compostos Orgânicos , Eliminação de Resíduos , Resíduos Sólidos , Compostagem/métodos , Eliminação de Resíduos/métodos , Compostos Orgânicos/análise , Resíduos Sólidos/análise , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Esterco , Proteobactérias , Microbiota
13.
World J Clin Cases ; 12(17): 2976-2982, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38898850

RESUMO

BACKGROUND: Diabetic foot ulcers (DFUs) are a common complication of diabetes, often leading to severe infections, amputations, and reduced quality of life. The current standard treatment protocols for DFUs have limitations in promoting efficient wound healing and preventing complications. A comprehensive treatment approach targeting multiple aspects of wound care may offer improved outcomes for patients with DFUs. The hypothesis of this study is that a comprehensive treatment protocol for DFUs will result in faster wound healing, reduced amputation rates, and improved overall patient outcomes compared to standard treatment protocols. AIM: To compare the efficacy and safety of a comprehensive treatment protocol for DFUs with those of the standard treatment protocol. METHODS: This retrospective study included 62 patients with DFUs, enrolled between January 2022 and January 2024, randomly assigned to the experimental (n = 32) or control (n = 30) group. The experimental group received a comprehensive treatment comprising blood circulation improvement, debridement, vacuum sealing drainage, recombinant human epidermal growth factor and anti-inflammatory dressing, and skin grafting. The control group received standard treatment, which included wound cleaning and dressing, antibiotics administration, and surgical debridement or amputation, if necessary. Time taken to reduce the white blood cell count, number of dressing changes, wound healing rate and time, and amputation rate were assessed. RESULTS: The experimental group exhibited significantly better outcomes than those of the control group in terms of the wound healing rate, wound healing time, and amputation rate. Additionally, the comprehensive treatment protocol was safe and well tolerated by the patients. CONCLUSION: Comprehensive treatment for DFUs is more effective than standard treatment, promoting granulation tissue growth, shortening hospitalization time, reducing pain and amputation rate, improving wound healing, and enhancing quality of life.

14.
J Org Chem ; 89(12): 8531-8536, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38838346

RESUMO

An effective multicomponent reaction for the synthesis of 4-phosphorylated 4H-chromenes via a tandem phosphorylation/alkylation/cyclization/dehydration sequence with water as the only byproduct was developed. Extensive mechanistic investigations involving in situ NMR experiments, time control experiments, and in situ HRMS experiment allowed us to elucidate the order of each subreaction to arrive at a complete understanding of the underlying mechanism of this multicomponent reaction. Mechanistic data confirm that the reaction begins with a phospha-aldol-elimination, followed by addition of a ketone enolate, intermolecular alkylation, intramolecular cyclization, and dehydration under acidic conditions.

15.
ACS Appl Mater Interfaces ; 16(24): 30671-30684, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38843203

RESUMO

Indoleamine 2,3-dioxygenase (IDO), highly expressed in hepatocellular carcinoma (HCC), plays a pivotal role in creating an immune-suppressive tumor microenvironment. Inhibiting IDO activity has emerged as a promising immunotherapeutic strategy; however, the delivery of IDO inhibitors to the tumor site is constrained, limiting their therapeutic efficacy. In this study, we developed a magnetic vortex nanodelivery system for the targeted delivery of the IDO inhibitor NLG919, integrated with magnetic hyperthermia therapy to reverse the immune-suppressive microenvironment of liver cancer and inhibit tumor growth. This system comprises thermoresponsive polyethylenimine-coated ferrimagnetic vortex-domain iron oxide nanorings (PI-FVIOs) loaded with NLG919 (NLG919/PI-FVIOs). Under thermal effects, NLG919 can be precisely released from the delivery system, counteracting IDO-mediated immune suppression and synergizing with NLG919/PI-FVIOs-mediated magnetothermodynamic (MTD) therapy-induced immunogenic cell death (ICD), resulting in effective HCC suppression. In vivo studies demonstrate that this combination therapy significantly inhibits tumor growth and metastasis by enhancing the accumulation of cytotoxic T lymphocytes and suppressing regulatory T cells within the tumor. Overall, our findings reveal that NLG919/PI-FVIOs can induce a potent antitumor immune response by disrupting the IDO pathway and activating the ICD, offering a promising therapeutic avenue for HCC treatment.


Assuntos
Indolamina-Pirrol 2,3,-Dioxigenase , Neoplasias Hepáticas , Microambiente Tumoral , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Animais , Microambiente Tumoral/efeitos dos fármacos , Camundongos , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/imunologia , Hipertermia Induzida , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Antineoplásicos/química , Antineoplásicos/farmacologia , Imidazóis , Isoindóis
16.
Cureus ; 16(5): e60130, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38864037

RESUMO

Neuropathic pain (NP), resulting from damage to the somatosensory system, is characterized by either spontaneous or evoked pain. In the context of NP, wherein aberrant signaling pathways contribute to the perception of pain, the thalamus emerges as a key player. This structure is integral to the pain network that includes connections to the dorsal horn of the spinal cord, highlighting its role in the affective-motivational aspects of pain perception. Given its significant involvement, the thalamus is targeted in advanced treatments such as thalamotomy and deep brain stimulation (DBS) when traditional therapies fail, emphasizing the need to understand its function in NP to improve management strategies. This review aimed to provide an overview of the role of the thalamus in the transmission of nociceptive information in NP by discussing the existing evidence, including the effectiveness and safety of current techniques in the management and treatment of NP. This is an integrative review involving the qualitative analysis of scientific articles published in PubMed/MEDLINE, Embase, Scopus, and Web of Science. A total of 687 articles were identified, and after selection, 15 articles were included in this study. All studies reviewed demonstrated varying degrees of effectiveness of DBS and thalamotomy in alleviating painful symptoms, although the relief was often temporary. Many studies noted a reduction in pain perception at the conclusion of treatment compared to pre-treatment levels, with this decrease maintained throughout patient follow-ups. However, adverse events associated with these treatments were also reported. In conclusion, there are some benefits, albeit temporary, to using thalamotomy and DBS to alleviate the painful symptoms of NP. Both procedures are considered advanced forms of surgical intervention that aim to modulate pain pathways in the brain, providing significant relief for patients suffering from chronic pain resistant to conventional treatment. Despite limitations, these surgical interventions offer renewed hope for patients facing disabling chronic pain and can provide a significant improvement in quality of life.

17.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2689-2698, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812169

RESUMO

This study aims to prepare co-loaded indocyanine green(ICG) and elemene(ELE) nano-emulsion(NE) in situ gel(ICG-ELE-NE-gel) and evaluate its physicochemical properties and antitumor activity in vitro. ICG-ELE-NE-gel was prepared by aqueous phase titration and cold solution methods, followed by characterization of the morphology, particle size, corrosion, and photothermal conversion characteristics. The human breast cancer MCF-7 cells were taken as the model, combined with 808 nm laser irradia-tion. Cell inhibition rate test and cell uptake test were performed. ICG-ELE-NE was spherical and uniform in size. The average particle size and Zeta potential were(85.61±0.35) nm and(-21.4±0.6) mV, respectively. The encapsulation efficiency and drug loading rate were 98.51%±0.39% and 10.96%±0.24%, respectively. ICG-ELE-NE-gel had a good photothermal conversion effect and good photothermal stability. The dissolution of ICG-ELE-NE-gel had both temperature and pH-responsive characteristics. Compared with free ELE, ICG-ELE-NE-gel combined with near-infrared light irradiation significantly enhanced the inhibitory effect on MCF-7 cells and could be uptaken in large amounts by MCF-7 cells. ICG-ELE-NE-gel was successfully prepared, and its antitumor activity was enhanced after 808 nm laser irradiation.


Assuntos
Neoplasias da Mama , Proliferação de Células , Emulsões , Verde de Indocianina , Humanos , Verde de Indocianina/química , Células MCF-7 , Emulsões/química , Proliferação de Células/efeitos dos fármacos , Feminino , Tamanho da Partícula , Géis/química , Nanopartículas/química , Composição de Medicamentos/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Portadores de Fármacos/química
18.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1793-1801, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38812191

RESUMO

Soil nutrients and inorganic elements affect not only the growth and development of medicinal plants but also the formation and accumulation of active ingredients in traditional Chinese medicines. The content of tanshinones and 28 inorganic elements in Salviae Miltiorrhizae Radix et Rhizoma samples from 18 producing areas in 6 provinces was determined, and 35 physical and chemical properties of the corresponding soil samples were determined. The enrichment characteristics of inorganic elements in Salviae Miltiorrhizae Radix et Rhizoma were analyzed. The correlation analysis and stepwise regression analysis were performed to screen out the main soil factors affecting the content of tanshinones in Salviae Miltiorrhizae Radix et Rhizoma. The results showed that the content of tanshinones in the samples from different areas varied significantly, being the highest in the samples from Shandong, the second in the samples from Henan, and low in the samples from Shanxi and Sichuan. K, Mg, Ca, and Na were rich in Salviae Miltiorrhizae Radix et Rhizoma samples, among which Na and K had the highest enrichment coefficients. The results of correlation and regression analyses showed that soil K, Na, Ti, and total nitrogen were the main soil factors affecting the tanshinones in Salviae Miltiorrhizae Radix et Rhizoma. Specifically, the content of tanshinones was positively correlated with Ti and negatively correlated with Na, K, and total nitrogen in the soil. Therefore, during the planting of Salvia miltiorrhiza, the land should be selected with full consideration to the salinity and saline land should be avoided. Secondly, the application of nitrogen and potassium fertilizers can be appropriately reduced, and water-soluble elemental fertilizers for S. miltiorrhiza should be developed.


Assuntos
Abietanos , Rizoma , Salvia miltiorrhiza , Solo , Salvia miltiorrhiza/química , Abietanos/análise , Solo/química , Rizoma/química , China , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Nitrogênio/análise
19.
Int Immunopharmacol ; 134: 112188, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38728880

RESUMO

Neuroinflammation is one of the extensive secondary injury processes that aggravate metabolic and cellular dysfunction and tissue loss following spinal cord injury (SCI). Thus, an anti-inflammatory strategy is crucial for modulating structural and functional restoration during the stage of acute and chronic SCI. Recombinant fibroblast growth factor 4 (rFGF4) has eliminated its mitogenic activity and demonstrated a metabolic regulator for alleviating hyperglycemia in type 2 diabetes and liver injury in non-alcoholic steatohepatitis. However, it remains to be explored whether or not rFGF4 has a neuroprotective effect for restoring neurological disorders, such as SCI. Here, we identified that rFGF4 could polarize microglia/macrophages into the restorative M2 subtype, thus exerting an anti-inflammatory effect to promote neurological functional recovery and nerve fiber regeneration after SCI. Importantly, these effects by rFGF4 were related to triggering PI3K/AKT/GSK3ß and attenuating TLR4/NF-κB signaling axes. Conversely, gene silencing of the PI3K/AKT/GSK3ß signaling or pharmacological reactivation of the TLR4/NF-κB axis aggravated inflammatory reaction. Thus, our findings highlight rFGF4 as a potentially therapeutic regulator for repairing SCI, and its outstanding effect is associated with regulating macrophage/microglial polarization.


Assuntos
Glicogênio Sintase Quinase 3 beta , Macrófagos , Microglia , NF-kappa B , Regeneração Nervosa , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Microglia/efeitos dos fármacos , Microglia/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Regeneração Nervosa/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , NF-kappa B/metabolismo , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos , Masculino , Axônios/metabolismo , Axônios/efeitos dos fármacos , Axônios/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos Endogâmicos C57BL , Ratos Sprague-Dawley , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fenótipo , Ratos , Humanos , Modelos Animais de Doenças , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia
20.
Int J Biol Macromol ; 271(Pt 1): 132605, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38788869

RESUMO

Natural preservatives such as cinnamaldehyde (CIN) are garnering increasing interest to replace their synthetic counterparts in maintaining fruit freshness and safety. However, their long-term effectiveness and widespread application have been greatly limited due to high volatility and potent aroma. To address these challenges, we developed a viable and simple strategy to prepare a multifunctional active coating for fruit preservation by incorporating host-guest inclusion complex of CIN and 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) CIN@HP-ß-CD into hyaluronic acid (HA), a natural polysaccharide with exceptional film-forming properties. The as-prepared HA/CIN@HP-ß-CD coatings exhibited universal surface affinity, excellent antimicrobial performance, and satisfactory antioxidant properties with no potential toxicity. Release kinetic studies have demonstrated that CIN in the coating is continuously and slowly released. Furthermore, freshness preservation experiments on bananas and fresh-cut apples demonstrated that the developed coating is effective in preserving the color of fruit, decreasing the weight loss rate, preventing the microorganism's growth, and significantly extending the period of freshness, exhibiting the potential for application in fruit preservation.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina , Acroleína , Conservação de Alimentos , Frutas , Ácido Hialurônico , Acroleína/análogos & derivados , Acroleína/química , Acroleína/farmacologia , Frutas/química , 2-Hidroxipropil-beta-Ciclodextrina/química , Conservação de Alimentos/métodos , Ácido Hialurônico/química , Antioxidantes/química , Antioxidantes/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia
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