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1.
Zhongguo Zhong Yao Za Zhi ; 49(4): 884-893, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621895

RESUMO

Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Sepse , Humanos , Medicina Tradicional Chinesa , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Sepse/complicações , Sepse/tratamento farmacológico , Apoptose , Transdução de Sinais , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia
2.
Chemosphere ; 355: 141834, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38565376

RESUMO

Membrane fouling caused by the organics-coated particles was the main obstacle for the highly efficient shale gas produced water (SGPW) treatment and recycling. In this study, a novel hybrid electrocoagulation (EC) and E-peroxone process coupled with UF (ECP-UF) process was proposed to examine the efficacy and elucidate the mechanism for UF fouling mitigation in assisting SGPW reuse. Compared to the TMP (transmembrane pressure) increase of -15 kPa in the EC-UF process, TMP in ECP-UF system marginally increased to -1.4 kPa for 3 filtration cycles under the current density of 15 mA/cm2. Both the total fouling index and hydraulically irreversible fouling index of the ECP-UF process were significantly lower than those of EC-UF process. According to the extended Derjaguin-Landau-Verwey-Overbeek theory, the potential barriers was the highest for ECP-UF processes due to the substantial increase of the acid-base interaction energy in ECP-UF process, which was well consistent with the TMP and SEM results. Turbidity and TOC of ECP-UF process were 63.6% and 45.8% lower than those of EC-UF process, respectively. According to the MW distribution, the variations of compounds and their relative contents were probably due to the oxidation and decomposing products of the macromolecular organics. The number of aromatic compound decreased, while the number of open-chain compounds (i.e., alkenes, alkanes and alcohols) increased in the permeate of ECP-UF process. Notably, the substantial decrease in the relative abundance of di-phthalate compounds was attributed to the high reactivity of these compounds with ·OH. Mechanism study indicated that ECP could realize the simultaneous coagulation, H2O2 generation and activation by O3, facilitating the enhancement of ·OH and Alb production and therefore beneficial for the improved water quality and UF fouling mitigation. Therefore, the ECP-UF process emerges as a high-efficient and space-saving approach, yielding a synergistic effect in mitigating UF fouling for SGPW recycling.

3.
Eur J Med Res ; 29(1): 215, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38566152

RESUMO

OBJECTIVE: To compare the fluid resuscitation effect of sodium acetate Ringer's solution and sodium bicarbonate Ringer's solution on patients with traumatic haemorrhagic shock. METHOD: We conducted a prospective cohort study in our emergency department on a total of 71 patients with traumatic haemorrhagic shock admitted between 1 December 2020 and 28 February 2022. Based on the time of admission, patients were randomly divided into a sodium bicarbonate Ringer's solution group and sodium acetate Ringer's solution group, and a limited rehydration resuscitation strategy was adopted in both groups. General data were collected separately, and the patients' vital signs (body temperature, respiration, blood pressure and mean arterial pressure (MAP)), blood gas indices (pH, calculated bicarbonate (cHCO3-), partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (pCO2) and clearance of lactate (CLac)), shock indices, peripheral platelet counts, prothrombin times and plasma fibrinogen levels were measured and compared before and 1 h after resuscitation. RESULTS: The post-resuscitation heart rate of the sodium bicarbonate Ringer's solution group was significantly lower than that of the sodium acetate Ringer's solution group (p < 0.05), and the MAP was also significantly lower (p < 0.05). The patients in the sodium bicarbonate Ringer's solution group had significantly higher pH, cHCO3- and PaO2 values and lower pCO2 and CLac values (p < 0.05) than those in the sodium acetate Ringer's solution group, and the post-resuscitation peripheral platelet counts and fibrinogen levels were significantly higher, with shorter plasma prothrombin times and smaller shock indices (p < 0.001). CONCLUSION: Sodium bicarbonate Ringer's solution is beneficial for maintaining MAP at a low level after resuscitation. The use of sodium bicarbonate Ringer's solution in limited fluid resuscitation has positive results and is of high clinical value.


Assuntos
Solução de Ringer , Choque Hemorrágico , Humanos , Fibrinogênio , Hemorragia , Estudos Prospectivos , Ressuscitação/métodos , Solução de Ringer/uso terapêutico , Choque Hemorrágico/tratamento farmacológico , Acetato de Sódio , Bicarbonato de Sódio
4.
Phys Chem Chem Phys ; 26(15): 11968-11979, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38573242

RESUMO

Electromagnetic waves can cause different degrees of damage to the human body. People are developing unique nanomaterials with excellent reflection loss (RL), thin thickness, wide frequency band and light weight to improve the absorption efficiency of electromagnetic waves. Using a hydrothermal method, ZnO nanocrystals are combined with graphene oxide (GO). After heat treatment, evenly dispersed ZnO nanocrystals are attached to the GO surface or inserted into the lamellae, and the amount of Zn(CH3COO)2·2H2O and GO is selected to obtain ZnO/RGO nanocomposites with different mass ratios (1 : 1, 1 : 2, 1 : 3). The ZnO/RGO nanocomposites were mixed with paraffin wax with different mass ratios (15, 20, 25, 30 wt%) to explore their electromagnetic parameters and wave absorption properties. It is found that at 25 wt%, ZnO : GO = 3 : 1 and thickness of 3 mm, the sample exhibits excellent wave absorption performance (-36.6 dB) and wide effective absorption bandwidth (6.6 GHz). The microwave absorption performance is enhanced because ZnO nanocrystals inhibit RGO agglomeration and improve impedance matching between the heterostructure interface and RGO.

5.
Hepatobiliary Pancreat Dis Int ; 23(2): 117-122, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38619051

RESUMO

Hepatectomy is still the major curative treatment for patients with liver malignancies. However, it is still a big challenge to remove the tumors in the central posterior area, especially if their location involves the retrohepatic inferior vena cava and hepatic veins. Ex vivo liver resection and auto-transplantation (ELRA), a hybrid technique of the traditional liver resection and transplantation, has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation. Due to its technical difficulty, ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation. The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases, especially in the advanced alveolar echinococcosis. Recently, the application of ELRA for liver malignances has gained more attention. However, standardization of clinical practice norms and international consensus are still lacking. The prognostic impact in these oncologic patients also needs further evaluation. In this review, we summarized the principles and recent progresses on ELRA.


Assuntos
Neoplasias Hepáticas , Transplante de Fígado , Humanos , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Consenso
6.
Lung Cancer ; 191: 107791, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38621342

RESUMO

OBJECTIVES: With the increasing popularity of CT screening, more cases of early-stage lung cancer are being diagnosed. However, 24.5% of stage I non-small-cell lung cancer (NSCLC) patients still experience treatment failure post-surgery. Biomarkers to predict lung cancer patients at high risk of recurrence are needed. MATERIALS AND METHODS: We collected protein mass spectrometry data from the Taiwan Lung Cancer Moonshot Project and performed bioinformatics analysis on proteins with differential expressions between tumor and adjacent normal tissues in 74 stage I lung adenocarcinoma (LUAD) cases, aiming to explore the tumor microenvironment related prognostic biomarkers. Findings were further validated in 6 external cohorts. RESULTS: The analysis of differentially expressed proteins revealed that the most enriched categories of diseases and biological functions were cellular movement, immune cell trafficking, and cancer. Utilizing proteomic profiling of the tumor microenvironment, we identified five prognostic biomarkers (ADAM10, MIF, TEK, THBS2, MAOA). We then developed a risk score model, which independently predicted recurrence-free survival and overall survival in stage I LUAD. Patients with high risk scores experienced worse recurrence-free survival (adjusted hazard ratio = 8.28, p < 0.001) and overall survival (adjusted hazard ratio = 6.88, p = 0.013). Findings had been also validated in the external cohorts. CONCLUSION: The risk score model derived from proteomic profiling of tumor microenvironment can be used to predict recurrence risk and prognosis of stage I LUAD.

7.
BMC Res Notes ; 17(1): 102, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594730

RESUMO

Immune checkpoint blockade (ICB) therapy holds promise for bringing long-lasting clinical gains for the treatment of cancer. However, studies show that only a fraction of patients respond to the treatment. In this regard, it is valuable to develop gene expression signatures based on RNA sequencing (RNAseq) data and machine learning methods to predict a patient's response to the ICB therapy, which contributes to more personalized treatment strategy and better management of cancer patients. However, due to the limited sample size of ICB trials with RNAseq data available and the vast number of candidate gene expression features, it is challenging to develop well-performed gene expression signatures. In this study, we used several published melanoma datasets and investigated approaches that can improve the construction of gene expression-based prediction models. We found that merging datasets from multiple studies and incorporating prior biological knowledge yielded prediction models with higher predictive accuracies. Our finding suggests that these two strategies are of high value to identify ICB response biomarkers in future studies.


Assuntos
Inibidores de Checkpoint Imunológico , Melanoma , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Conhecimento , Aprendizado de Máquina , RNA
8.
Mol Immunol ; 170: 19-25, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38598870

RESUMO

The assembly of tissue-damaging membrane attack complexes (MACs; C5b-9) is a major mechanism by which excessive complement activation causes diseases. We previously developed a mouse anti-human C6 monoclonal antibody (mAb) 1C9 that selectively inhibits the assembly of MACs in human and non-human primates. In this project, we found that 1C9 also cross-reacted with rat and guinea pig C6, and determined its binding domains on C6 using different truncated C6 proteins. We then humanized the anti-C6 mAb by molecular modeling and complementarity-determining region grafting. After screening a library of 276 humanized variants with different combinations of humanized light and heavy chains in biophysical assays, we identified clone 3713 with the best developability profile, and an increased affinity against C6 when compared with the parental 1C9 mAb. This humanized 3713 mAb inhibited human, monkey, and rat complement-mediated hemolysis in vitro, and more importantly, it significantly reduced complement-mediated hemolysis in vivo in rats. These results demonstrated the successful humanization of the anti-C6 mAb and suggested that the humanized 3713 mAb could be further developed as a new therapeutic that selectively targets MAC for certain complement-mediated pathological conditions.

9.
Neuropharmacology ; 252: 109939, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38570065

RESUMO

To investigate the efficacy of Ursolic acid in alleviating neuropathic pain in rats with spinal nerve ligation (SNL), the SNL rat model was surgically induced. Different concentrations of Ursolic acid and manipulated target mitogen-activated protein kinase 1 (MAPK1) were administered to the SNL rats. Fecal samples were collected from each group of rats for 16S rDNA analysis to examine the impact of gut microbiota. Molecular docking experiments were conducted to assess the binding energy between Ursolic acid and MAPK1. In vivo studies were carried out to evaluate the expression of inflammatory factors and signaling pathways in spinal cord and colon tissues. Ursolic acid was found to have a beneficial effect on pain reduction in rats by increasing plantar withdrawal latency (PWL) and paw withdrawal threshold (PWT). Comparing the Ursolic acid group with the control group revealed notable differences in the distribution of Staphylococcus, Allobaculum, Clostridium, Blautia, Bifidobacterium, and Prevotella species. Network pharmacology analysis identified MAPK1 and intercellular adhesion molecule-1 (ICAM1) as common targets for Ursolic acid, SNL, and neuropathic pain. Binding sites between Ursolic acid and these targets were identified. Additionally, immunofluorescent staining showed a decrease in GFAP and IBA1 intensity in the spinal cord along with an increase in NeuN following Ursolic acid treatment. Overexpression of MAPK1 in SNL rats led to an increase in inflammatory factors and a decrease in PWL and PWT. Furthermore, MAPK1 counteracted the pain-relieving effects of Ursolic acid in SNL rats. Ursolic acid was found to alleviate neuropathic pain in SNL rats by targeting MAPK1 and influencing gut microbiota homeostasis.

10.
Heliyon ; 10(7): e28312, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38571578

RESUMO

Hydropower stations that are part of the grid system frequently encounter challenges related to the uneven distribution of power generation and associated benefits, primarily stemming from delays in obtaining timely load data. This research addresses this issue by developing a scheduling model that combines power load prediction and dual-objective optimization. The practical application of this model is demonstrated in a real-case scenario, focusing on the Shatuo Hydropower Station in China. In contrast to current models, the suggested model can achieve optimal dispatch for grid-connected hydropower stations even when power load data is unavailable. Initially, the model assesses various prediction models for estimating power load and subsequently incorporates the predictions into the GA-NSGA-II algorithm, specifically an enhanced elite non-dominated sorting genetic algorithm. This integration is performed while considering the proposed objective functions to optimize the discharge flow of the hydropower station. The outcomes reveal that the CNN-GRU model, denoting Convolutional Neural Network-Gated Recursive Unit, exhibits the highest prediction accuracy, achieving R-squared and RMSE (i.e., Root Mean Square Error) values of 0.991 and 0.026, respectively. The variance between scheduling based on predicted load values and actual load values is minimal, staying within 5 (m3/s), showcasing practical effectiveness. The optimized scheduling outcomes in the real case study yield dual advantages, meeting both the demands of ship navigation and hydropower generation, thus achieving a harmonious balance between the two requirements. This approach addresses the real-world challenges associated with delayed load data collection and insufficient scheduling, offering an efficient solution for managing hydropower station scheduling to meet both power generation and navigation needs.

11.
Sci Rep ; 14(1): 8095, 2024 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582932

RESUMO

Legumain (or asparagine endopeptidase/AEP) is a lysosomal cysteine endopeptidase associated with increased invasive and migratory behavior in a variety of cancers. In this study, co-delivery of Cas9 mRNA and guide RNA (gRNA) by lipid nanoparticles (LNP) for editing of LGMN gene was performed. For in-vitro transcription (IVT) of gRNA, two templates were designed: linearized pUC57-T7-gRNA and T7-gRNA oligos, and the effectiveness of gRNA was verified in multiple ways. Cas9 plasmid was modified and optimized for IVT of Cas9 mRNA. The effects of LGMN gene editing on lysosomal/autophagic function and cancer cell metastasis were investigated. Co-delivery of Cas9 mRNA and gRNA resulted in impaired lysosomal/autophagic degradation, clone formation, migration, and invasion capacity of cancer cells in-vitro. Experimental lung metastasis experiment indicates co-delivery of Cas9 mRNA and gRNA by LNP reduced the migration and invasion capacity of cancer cells in-vivo. These results indicate that co-delivery of Cas9 mRNA and gRNA can enhance the efficiency of CRISPR/Cas9-mediated gene editing in-vitro and in-vivo, and suggest that Cas9 mRNA and gRNA gene editing of LGMN may be a potential treatment for breast tumor metastasis.


Assuntos
Neoplasias da Mama , Sistemas CRISPR-Cas , Humanos , Feminino , Sistemas CRISPR-Cas/genética , RNA Guia de Sistemas CRISPR-Cas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias da Mama/genética , Edição de Genes/métodos
12.
Nat Neurosci ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589584

RESUMO

Learning and memory require activity-induced changes in dendritic translation, but which mRNAs are involved and how they are regulated are unclear. In this study, to monitor how depolarization impacts local dendritic biology, we employed a dendritically targeted proximity labeling approach followed by crosslinking immunoprecipitation, ribosome profiling and mass spectrometry. Depolarization of primary cortical neurons with KCl or the glutamate agonist DHPG caused rapid reprogramming of dendritic protein expression, where changes in dendritic mRNAs and proteins are weakly correlated. For a subset of pre-localized messages, depolarization increased the translation of upstream open reading frames (uORFs) and their downstream coding sequences, enabling localized production of proteins involved in long-term potentiation, cell signaling and energy metabolism. This activity-dependent translation was accompanied by the phosphorylation and recruitment of the non-canonical translation initiation factor eIF4G2, and the translated uORFs were sufficient to confer depolarization-induced, eIF4G2-dependent translational control. These studies uncovered an unanticipated mechanism by which activity-dependent uORF translational control by eIF4G2 couples activity to local dendritic remodeling.

13.
Plant Dis ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587792

RESUMO

Euphorbia lathyris L. is a biennial herb in the Euphorbiaceae that has been used as a medicinal plant. It is distributed or cultivated worldwide, and the seeds of E. lathyris are the main source of ingenol, which is the precursor of Picato, the first medicine approved by USFDA for the treatment of solar keratosis (Abramovits et al. 2013). However, the production of E. lathyris can be severely hampered by the occurrence of plant diseases. Between 2020-2022 (specifically in October-November of each year), anthracnose-like symptoms were observed on E. lathyris in fields (E 118°49'50″, N 32°3'33″) in Nanjing, Jiangsu Province, China. The incidence of E. lathyris with disease symptoms was between 25%-30% (n = 100). The lesions on the leaves were evident initially as dark brown spots, which expanded into larger necrotic spots, finally resulting in leaves withering and dropping off. In severe cases, stem wilting was also observed. To determine the causal agent, we collected diseased leaf samples (n = 20) from different E. lathyris plants in the field (~ 1800 m2). After cleaning, the junctions of the diseased and healthy parts were excised and sterilized in 75% ethanol for 20-25 seconds, and rinsed with sterile water. After that, they were transferred onto potato sucrose agar (PSA) plates and placed at 25℃ for 3-4 days, until fungal growth was evident. The fungus was purified by recovering single conidia and growing them on PSA (Hu et al. 2015). A consistent fungal colony, based on morphological characteristics, was recovered from 17 samples. The colony color was initially white, green in the middle, and gradually changed into gray green as the colony matured. Conidia were transparent and cylindrical (22-28 µm × 7-9 µm, n = 50). Five loci informative (ITS, TUB, ACT, GAPDH, and CHS-1) (Weir et al. 2012) for Colletotrichum spp. identification were sequenced from two isolates ELC-1 and ELC-2 obtained from different plant individuals. Compared with a reference isolate (Colletotrichum gloeosporioides ZH3), the GAPDH, CHS-1, and TUB2 sequences of ELC-1 and ELC-2 showed 95% (263 bp out of 275 bp), 98% (295 bp out of 299 bp), and 99% (711 bp out of 712 bp and 717 bp out of 719 bp) similarity, respectively. The ITS sequence identities were 100% (577 bp out of 577 bp) and 99% (594 bp out of 597 bp), while the ACT sequence identities were 100% (281 bp out of 281 bp) and 98% (279 bp out of 284 bp). All sequences have been deposited in Genbank database (OR865865-OR865866 and OR873625-OR873632). After performing phylogenetic analysis with Mega 11, the pathogen was confirmed as C. gloeosporioides. To fulfil Koch's postulates, we sprayed six-week-old healthy plants with a conidia suspension of C. gloeosporioides (106 spores/mL) or sterile water (serve as control). The inoculated plants were placed at 25℃, 100% relative humidity, and 12-h photoperiod (Zhang et al. 2021). Six plants were inoculated for each treatment, and the experiment was repeated three times. After 6-8 days, the plants inoculated with C. gloeosporioides showed similar symptoms to those observed on diseased plants in the field, while the control plants remained healthy and free of disease. The pathogens were then re-isolated and identified as C. gloeosporioides. To our knowledge, this is the first report of C. gloeosporioides causing anthracnose on E. lathyris. Anthracnose may cause significant yield losses in E. lathyris production, and our results will provide experimental and theoretical basis for the management of the disease.

14.
World J Gastroenterol ; 30(9): 1177-1188, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577193

RESUMO

BACKGROUND: Acute decompensation (AD) of cirrhosis is associated with high short-term mortality, mainly due to the development of acute-on-chronic liver failure (ACLF). Thus, there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is released from activated innate immune cells and correlated with various inflammatory processes. AIM: To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis. METHODS: A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort (n = 309) and validation cohort (n = 133). Demographic and clinical data were collected, and serum sTREM-1 was measured at admission. All enrolled patients were followed-up for at least 1 year. RESULTS: In patients with AD and cirrhosis, serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver, coagulation, cerebral and kidney failure. A new prognostic model of AD (P-AD) incorporating sTREM-1, blood urea nitrogen (BUN), total bilirubin (TBil), international normalized ratio (INR) and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease (MELD), MELD-sodium (MELD-Na), chronic liver failure-consortium (CLIF-C) ACLF and CLIF-C AD scores. Additionally, sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up. The ACLF risk score incorporating serum sTREM-1, BUN, INR, TBil and aspartate aminotransferase levels was established and significantly superior to MELD, MELD-Na, CLIF-C ACLF, CLIF-C AD and P-AD in predicting risk of ACLF development. CONCLUSION: Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.


Assuntos
Insuficiência Hepática Crônica Agudizada , Doença Hepática Terminal , Humanos , Insuficiência Hepática Crônica Agudizada/etiologia , Insuficiência Hepática Crônica Agudizada/complicações , Receptor Gatilho 1 Expresso em Células Mieloides , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Biomarcadores
15.
bioRxiv ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617241

RESUMO

Tumor metastasis, the main cause of death in cancer patients, requires outgrowth of tumor cells after their dissemination and residence in microscopic niches. Nutrient sufficiency is a determinant of such outgrowth 1 . Fatty acids (FA) can be metabolized by cancer cells for their energetic and anabolic needs but impair the cytotoxicity of T cells in the tumor microenvironment (TME) 2, 3 , thereby supporting metastatic progression. However, despite the important role of FA in metastatic outgrowth, the regulation of intratumoral FA is poorly understood. In this report, we show that tumor endothelium actively promotes tumor growth and restricts anti-tumor cytolysis by transferring FA into developing metastatic tumors. This process uses transendothelial fatty acid transport via endosome cargo trafficking in a mechanism that requires mTORC1 activity. Thus, tumor burden was significantly reduced upon endothelial-specific targeted deletion of Raptor, a unique component of the mTORC1 complex (Rptor ECKO ). In vivo trafficking of a fluorescent palmitic acid analog to tumor cells and T cells was reduced in Rptor ECKO lung metastatic tumors, which correlated with improved markers of T cell cytotoxicity. Combination of anti-PD1 with RAD001/everolimus, at a low dose that selectively inhibits mTORC1 in endothelial cells 4 , impaired FA uptake in T cells and reduced metastatic disease, corresponding to improved anti-tumor immunity. These findings describe a novel mechanism of transendothelial fatty acid transfer into the TME during metastatic outgrowth and highlight a target for future development of therapeutic strategies.

16.
Clin Exp Dermatol ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618759

RESUMO

BACKGROUND: No trial of supramolecular salicylic acid (SSA) for chloasma is available yet. OBJECTIVE: The purpose of this study was to assess the efficacy and safety of Bole DA 30% supramolecular salicylic acid (SSA) combined with 10% niacinamide in treating chloasma. METHODS: This multicenter (n=15), randomized, double-blind, parallel placebo-controlled trial randomized the subjects (1:1) to Bole DA 30% SSA or placebo. The primary endpoint was the effective rate after 16 weeks using the modified melasma area severity index (mMASI) [(pretreatment-posttreatment)/pretreatment×100%]. RESULTS: This study randomized 300 subjects (150/group in the full analysis set, 144 and 147 in the per-protocol set). The total mMASI score, overall Griffiths 10 score, left Griffiths 10 score, and right Griffiths 10 score were significantly lower in the Bole DA 30% SSA group than in the placebo group (all P<0.001). One study drug-related AE and one study drug-unrelated adverse events (AE) were reported in the Bole DA 30% SSA group. No AE was reported in the placebo group. CONCLUSION: Bole DA 30% SSA combined with 10% niacinamide is effective and safe for treating chloasma. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200065346.

17.
Biotechnol Bioeng ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38595326

RESUMO

Pathogenic bacterial membrane proteins (MPs) are a class of vaccine and antibiotic development targets with widespread clinical application. However, the inherent hydrophobicity of MPs poses a challenge to fold correctly in living cells. Herein, we present a comprehensive method to improve the soluble form of MP antigen by rationally designing multi-epitope chimeric antigen (ChA) and screening two classes of protein-assisting folding element. The study uses a homologous protein antigen as a functional scaffold to generate a ChA possessing four epitopes from transferrin-binding protein A of Glaesserella parasuis. Our engineered strain, which co-expresses P17 tagged-ChA and endogenous chaperones groEL-ES, yields a 0.346 g/L highly soluble ChA with the property of HPS-positive serum reaction. Moreover, the protein titer of ChA reaches 4.27 g/L with >90% soluble proportion in 5-L bioreactor, which is the highest titer reported so far. The results highlight a timely approach to design and improve the soluble expression of MP antigen in industrially viable applications.

18.
Neurosci Bull ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558365

RESUMO

Obstructive sleep apnea-hypopnea syndrome (OSAHS) significantly impairs children's growth and cognition. This study aims to elucidate the pathophysiological mechanisms underlying OSAHS in children, with a particular focus on the alterations in cortical information interaction during respiratory events. We analyzed sleep electroencephalography before, during, and after events, utilizing Symbolic Transfer Entropy (STE) for brain network construction and information flow assessment. The results showed a significant increase in STE after events in specific frequency bands during N2 and rapid eye movement (REM) stages, along with increased STE during N3 stage events. Moreover, a noteworthy rise in the information flow imbalance within and between hemispheres was found after events, displaying unique patterns in central sleep apnea and hypopnea. Importantly, some of these alterations were correlated with symptom severity. These findings highlight significant changes in brain region coordination and communication during respiratory events, offering novel insights into OSAHS pathophysiology in children.

19.
Front Bioeng Biotechnol ; 12: 1363742, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558788

RESUMO

In recent years, stem cells and their secretomes, notably exosomes, have received considerable attention in biomedical applications. Exosomes are cellular secretomes used for intercellular communication. They perform the function of intercellular messengers by facilitating the transport of proteins, lipids, nucleic acids, and therapeutic substances. Their biocompatibility, minimal immunogenicity, targetability, stability, and engineerable characteristics have additionally led to their application as drug delivery vehicles. The therapeutic efficacy of exosomes can be improved through surface modification employing functional molecules, including aptamers, antibodies, and peptides. Given their potential as targeted delivery vehicles to enhance the efficiency of treatment while minimizing adverse effects, exosomes exhibit considerable promise. Stem cells are considered advantageous sources of exosomes due to their distinctive characteristics, including regenerative and self-renewal capabilities, which make them well-suited for transplantation into injured tissues, hence promoting tissue regeneration. However, there are notable obstacles that need to be addressed, including immune rejection and ethical problems. Exosomes produced from stem cells have been thoroughly studied as a cell-free strategy that avoids many of the difficulties involved with cell-based therapy for tissue regeneration and cancer treatment. This review provides an in-depth summary and analysis of the existing knowledge regarding exosomes, including their engineering and cardiovascular disease (CVD) treatment applications.

20.
Epilepsy Behav ; 154: 109738, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38513572

RESUMO

BACKGROUND: Although sleep quality (SQ) reportedly affects the health-related quality of life (QOL) of patients with epilepsy, little is known about the potential association between SQ and QOL, particularly in children with epilepsy (CWE). Our study aimed to investigate the mediating effect of SQ on the QOL of CWE to obtain more information for the prevention and treatment of epilepsy in children. METHODS: We collected general demographic and clinical data of 212 CWE and 79 controls (children who visited the Health Examination Department), and their guardians were instructed to answer the Children's Sleep Habits Questionnaire (CSHQ) and the optimized Quality of Life in Childhood Epilepsy Questionnaire-16 (QOLCE-16). The t-test, analysis of variance, chi-square test, and Fisher's exact test were used for between group comparisons. The Pearson correlation was used to analyze the correlation between variables. The direct, indirect, and total effects of predictors on the QOL of CWE were estimated based on an adjusted mediation model. RESULTS: CWE had significantly smaller long-term urban residence rates, less educated guardians, higher total CSHQ score, higher incidence of poor SQ, higher bedtime resistance, more sleep anxiety, worse sleep-disordered breathing, increased parasomnia, more daytime sleepiness, more frequent night waking, and greater sleep onset delay than controls (P < 0.05 for all). The univariable analysis showed significant differences in total CSHQ scores between CWE with different seizure frequency in the last month, whether or not drug-resistant epilepsy (DRE), and with different video electroencephalogram (VEEG) findings (P < 0.05 for all). Differences in QOLCE-16 scores between CWE with different guardian's employment status, age at diagnosis, number of anti-seizure medication (ASM) types, seizure frequency in the last month, DRE status, seizure type, VEEG findings, neuropsychological evaluation findings, magnetic resonance imaging (MRI) findings, and etiology were statistically significant (P < 0.05 for all). The correlation study indicated that the total CSHQ score was negatively correlated with the QOLCE-16 score (P < 0.05). The mediation analysis showed that DRE and VEEG abnormalities had a standardized direct effect on the QOL. Seizure frequency in the last month, DRE, and VEEG abnormalities had an indirect effect on the QOL through SQ, and their mediating effect values of SQ were 31.61 %, 13.45 %, and 14.35 %, respectively. CONCLUSION: Our findings uncovered the relationship of some clinical characteristics with SQ and QOL and characterized the nature of factors affecting the QOL of CWE. SQ could be a key factor in the prognosis of CWE experiencing epileptic seizures, and more attention should be paid on the management of SQ in interventions for epilepsy.

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