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1.
J Clin Ultrasound ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38840562

RESUMO

Non-Hodgkin lymphoma (NHL) is a highly aggressive malignant tumor arising in lymph nodes or extra-nodal lymphoid tissues, with an incidence of 8.3 per million. It accounts for approximately 7% of childhood and adolescent malignancies, second only to leukemia and brain tumors. Despite the gastrointestinal tract being the most common extra-nodal site involved by lymphoma, primary intestinal lymphoma (PIL) is rare and typically affects middle-aged men without specific clinical symptoms. Here, we present the case of a 2-year-old child indicative of PIL with the informed consent of the parents.

2.
Metab Brain Dis ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842661

RESUMO

Subarachnoid hemorrhage (SAH) is a serious hemorrhagic event with high mortality and morbidity. Multiple injurious events produced by SAH can lead to a series of pathophysiologic processes in the hypothalamus that can severely impact patients' life. These pathophysiologic processes usually result in physiologic derangements and dysfunction of the brain and multiple organs. This dysfunction involved multiple dimensions of the genome and metabolome. In our study, we induced the SAH model in rats to obtain hypothalamic tissue and serum. The samples were subsequently analyzed by transcriptomics and metabolomics. Next, the functional enrichment analysis of the differentially expressed genes and metabolites were performed by GO and KEGG pathway analysis. Through transcriptomic analysis of hypothalamus samples, 263 up-regulated differential genes, and 207 down-regulated differential genes were identified in SAH groups compared to Sham groups. In the KEGG pathway analysis, a large number of differential genes were found to be enriched in IL-17 signaling pathway, PI3K-Akt signaling pathway, and bile secretion. Liquid chromatography-mass spectrometry metabolomics technology was conducted on the serum of SAH rats and identified 11 up-regulated and 26 down-regulated metabolites in positive ion model, and 1 up-regulated and 10 down-regulated metabolites in negative ion model. KEGG pathways analysis showed that differentially expressed metabolites were mainly enriched in pathways of bile secretion and primary bile acid biosynthesis. We systematically depicted the neuro- and metabolism-related biomolecular changes occurring in the hypothalamus after SAH by performing transcriptomics and metabolomics studies. These biomolecular changes may provide new insights into hypothalamus-induced metabolic changes and gene expression after SAH.

4.
PLoS One ; 19(6): e0290858, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38833488

RESUMO

The tarnished plant bug, (TPB) Lygus lineolaris Palisot de Beauvois (Hemiptera: Miridae) is a key pest of cotton in the midsouth region and some areas of the eastern United States. Its control methods have been solely based on chemical insecticides which has contributed to insecticidal resistance and shortened residual periods for control of this insect pest. This study was conducted over a two-year period and examined the efficacy and residual effect of four commercial insecticides including lambda-cyhalothrin (pyrethroid), acephate (organophosphate), imidacloprid (neonicotinoid), and sulfoxaflor (sulfoxamine). The effectiveness and residual effects of these insecticides were determined by application on cotton field plots on four different dates during each season using three different concentrations (high: highest labeled commercial dose (CD), medium: 1/10 of the CD, low: 1/100 of the CD) on field cotton plots. Four groups of cotton leaves were randomly pulled from each treated plot and control 0-, 2-, 4-, 7-, and 9-days post treatment (DPT) and exposed to a lab colony of TPB adults. One extra leaf sample/ plot/ spray /DPT interval (0-2-4-7-9-11) during 2016 was randomly collected from the high concentration plots and sent to Mississippi State Chemical Laboratory for residual analysis. Mortality of TPB adults was greatest for those placed on leaves sprayed with the organophosphate insecticide with mortalities (%) of 81.7±23.4 and 63.3±28.8 (SE) 1-day after exposure (DAE) on leaves 0-DPT with the high concentration for 2016 and 2017, respectively, reaching 94.5±9.5 and 95.4±7.6 6-DAE each year. Mortality to all insecticides continued until 9 and 4-DPT for high and medium concentrations, respectively. However, organophosphate (39.4±28.6) and pyrethroid (24.4±9.9) exhibited higher mortality than sulfoxamine (10.6±6.6) and the neonicotinoid (4.0±1.5) 7-DAE on 9-DPT leaves with the high concentration. Based on our results using the current assay procedure, TPB adults were significantly more susceptible to contact than systemic insecticides and due to its residual effect, organophosphate could kill over 80% of the TPB population 7-DPT.


Assuntos
Gossypium , Inseticidas , Neonicotinoides , Nitrilas , Nitrocompostos , Fosforamidas , Piretrinas , Inseticidas/farmacologia , Gossypium/parasitologia , Animais , Piretrinas/farmacologia , Neonicotinoides/farmacologia , Mississippi , Nitrilas/farmacologia , Nitrocompostos/farmacologia , Controle de Insetos/métodos , Heterópteros/efeitos dos fármacos , Imidazóis/farmacologia , Hemípteros/efeitos dos fármacos , Compostos Organotiofosforados , Piridinas , Compostos de Enxofre
5.
BMJ Open ; 14(6): e084932, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830742

RESUMO

OBJECTIVES: This study aimed to investigate the current status of innovative behaviours among nurses in traditional Chinese medicine (TCM) hospitals using latent profile analysis, identify potential subgroups and their population characteristics and explore factors associated with different categories. DESIGN: Cross-sectional study. SETTING: Six TCM hospitals in Anhui, China. PARTICIPANTS: From 1 April 2023 to 31 July 2023, a total of 642 registered nurses with more than 1 year of work experience were recruited from the clinical departments of six TCM hospitals using a stratified cluster sampling method. 529 valid questionnaires were recovered, presenting a validity rate of 82.40%. PRIMARY AND SECONDARY OUTCOME MEASURES: Data were collected through online surveys containing a sociodemographic questionnaire, the Nurse Innovative Behaviour Scale, the Nurse Adversity Quotient Self-Evaluation Scale and the Conditions for Work Effectiveness Questionnaire-II. Latent profile analysis was performed to identify categorisation features of nurses' innovative behaviour in TCM hospitals. Multiple logistic regression analyses were used to investigate associated factors with profile membership. RESULTS: TCM hospital nurses' innovative behaviours were mainly classified into three types of latent profiles: low innovative behaviour (35.3%), moderate innovative behaviour (48.4%) and high innovative behaviour (16.3%). The results of multiple logistic regression analyses indicated that gender, monthly income, department, hospital level, position, nurse competency level, any training attended related to TCM knowledge and skills, adversity quotient level and structural empowerment level were the influencing factors for the potential profiles. CONCLUSIONS: The innovative behaviour of nurses in TCM hospitals can be classified into three categories. Studying the heterogeneity of the innovative behaviour of nurses in TCM hospitals and its associated factors provides evidence for nursing administrators and educators to develop individualised interventions based on each latent characteristic to improve the innovative behaviour of nurses in TCM hospitals. It is of great significance to the heritage and innovative development of TCM nursing.


Assuntos
Recursos Humanos de Enfermagem Hospitalar , Humanos , Estudos Transversais , China , Feminino , Adulto , Masculino , Inquéritos e Questionários , Recursos Humanos de Enfermagem Hospitalar/psicologia , Medicina Tradicional Chinesa , Atitude do Pessoal de Saúde , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros/psicologia
6.
Sci Rep ; 14(1): 13118, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849506

RESUMO

Quantum computing has already demonstrated great computational potential across multiple domains and has received more and more attention. However, due to the connectivity limitations of Noisy Intermediate-Scale Quantum (NISQ) devices, most of the quantum algorithms cannot be directly executed without the help of inserting SWAP gates. Nevertheless, more SWAP gates lead to a longer execution time and, inevitably, lower fidelity of the algorithm. To this end, this paper proposes an optimized qubit mapping algorithm based on a dynamic look-ahead strategy to minimize the number of SWAP gates inserted. Firstly, a heuristic algorithm is proposed based on maximizing physical qubit connectivity to generate the optimal initial qubit mapping, which reduces the need for logical qubit shifts during subsequent SWAP gate insertion. Secondly, in the form of directed acyclic graphs, we identify quantum gates that violate the constraints of physical coupling and insert SWAP gates to remap qubits, thereby overcoming the limitations of qubit interactions. Finally, the optimal SWAP gate insertion strategy is built by comparing the cost of different SWAP gate insertion strategies through a multi-window look-ahead strategy to reduce the number of SWAP gates inserted. The experimental results show that the strategy in this paper decreases the number of SWAP gate insertions and significantly reduces the depth of quantum circuits when performing qubit mapping compared with state-of-the-art methods.

7.
Phytomedicine ; 130: 155626, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38850631

RESUMO

BACKGROUND: Myocardial infarction (MI) is a serious cardiovascular disease, which presents different pathophysiological changes with the prolongation of the disease. Compound danshen dripping pills (CDDP) has obvious advantages in MI treatment and widely used in the clinic. However, the current studies were mostly focused on the endpoint of CDDP intervention, lacking the dynamic attention to the disease process. It is of great value to establish a dynamic research strategy focused on the changes in pharmacodynamic substances for guiding clinical medication more precisely. PURPOSE: It is aimed to explore the dynamic regulating pattern of CDDP on MI based on metabolic trajectory analysis, and then clarify the variation characteristic biomarkers and pharmacodynamic substances in the intervention process. METHODS: The MI model was successfully prepared by coronary artery left anterior descending branch ligation, and then CDDP intervention was given for 28 days. Endogenous metabolites and the components of CDDP in serum were measured by LC/MS technique simultaneously to identify dynamic the metabolic trajectory and screen the characteristic pharmacodynamic substances at different points. Finally, network pharmacology and molecular docking techniques were used to simulate the core pharmacodynamic substances and core target binding, then validated at the genetic and protein level by Q-PCR and western blotting technology. RESULTS: CDDP performed typical dynamic regulation features on metabolite distribution, biological processes, and pharmacodynamic substances. During 1-7 days, it mainly regulated lipid metabolism and inflammation, the Phosphatidylcholine (PC(18:1(9Z/18:1(9Z)) and Sphingomyelin (SM(d18:1/23:1(9Z)), SM(d18:1/24:1(15Z)), SM(d18:0/16:1(9Z))) were the main characteristic biomarkers. Lipid metabolism was the mainly regulation pathway during 14-21 days, and the characteristic biomarkers were the Lysophosphatidylethanolamine (LysoPE(0:0/20:0), PE-NMe2(22:1(13Z)/15:0)) and Sphingomyelin (SM(d18:1/23:1(9Z))). At 28 days, in addition to inflammatory response and lipid metabolism, fatty acid metabolism also played the most important role. Correspondingly, Lysophosphatidylcholine (LysoPC(20:0/0:0)), Lysophosphatidylserine (LPS(18:0/0:0)) and Fatty acids (Linoelaidic acid) were the characteristic biomarkers. Based on the results of metabolite distribution and biological process, the characteristic pharmacodynamic substances during the intervention were further identified. The results showed that various kinds of Saponins and Tanshinones as the important active ingredients performed a long-range regulating effect on MI. And the other components, such as Tanshinol and Salvianolic acid B affected Phosphatidylcholine and Sphingomyelin through Relaxin Signaling pathway during the early intervention. Protocatechualdehyde and Rosmarinic acid affected Lysophosphatidylethanolamine and Sphingomyelin through EGFR Tyrosine kinase inhibitor resistance during the late intervention. Tanshinone IIB and Isocryptotanshinone via PPAR signaling pathway affected Lysophosphatidylcholine, Lysophosphatidylserine, and Fatty acids. CONCLUSION: The dynamic regulating pattern was taken as the entry point and constructs the dynamic network based on metabolic trajectory analysis, establishes the dynamic correlation between the drug-derived components and the endogenous metabolites, and elucidates the characteristic biomarkers affecting the changes of the pharmacodynamic indexes, systematically and deeply elucidate the pharmacodynamic substance and mechanism of CDDP on MI. It also enriched the understanding of CDDP and provided a methodological reference for the dynamic analysis of complex systems of TCM.


Assuntos
Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Infarto do Miocárdio , Salvia miltiorrhiza , Medicamentos de Ervas Chinesas/farmacologia , Salvia miltiorrhiza/química , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Animais , Masculino , Farmacologia em Rede , Ratos Sprague-Dawley , Biomarcadores/metabolismo , Ratos , Lisofosfatidilcolinas , Canfanos , Panax notoginseng
8.
Microb Pathog ; 192: 106723, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823465

RESUMO

The Hedgehog (Hh) signaling pathway is involved in T cell differentiation and development and plays a major regulatory part in different stages of T cell development. A previous study by us suggested that prenatal exposure to staphylococcal enterotoxin B (SEB) changed the percentages of T cell subpopulation in the offspring thymus. However, it is unclear whether prenatal SEB exposure impacts the Hh signaling pathway in thymic T cells. In the present study, pregnant rats at gestational day 16 were intravenously injected once with 15 µg SEB, and the thymi of both neonatal and adult offspring rats were aseptically acquired to scrutinize the effects of SEB on the Hh signaling pathway. It firstly found that prenatal SEB exposure clearly caused the increased expression of Shh and Dhh ligands of the Hh signaling pathway in thymus tissue of both neonatal and adult offspring rats, but significantly decreased the expression levels of membrane receptors of Ptch1 and Smo, transcription factor Gli1, as well as target genes of CyclinD1, C-myc, and N-myc in Hh signaling pathway of thymic T cells. These data suggest that prenatal SEB exposure inhibits the Hh signaling pathway in thymic T lymphocytes of the neonatal offspring, and this effect can be maintained in adult offspring via the imprinting effect.


Assuntos
Enterotoxinas , Proteínas Hedgehog , Transdução de Sinais , Linfócitos T , Timo , Animais , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Feminino , Gravidez , Ratos , Timo/metabolismo , Timo/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , Receptor Patched-1/metabolismo , Receptor Patched-1/genética , Receptor Smoothened/metabolismo , Receptor Smoothened/genética , Efeitos Tardios da Exposição Pré-Natal/imunologia , Diferenciação Celular/efeitos dos fármacos , Ratos Sprague-Dawley , Masculino
9.
Talanta ; 277: 126388, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38870759

RESUMO

Metal organic cages (MOCs), as an emerging discrete supramolecular compounds, have received widespread attention in separation, biomedicine, gas capture, catalysis, and molecular recognition due to their porosity, adjustability and stability. Herein, we present a new chiral MOC FeII4L4 coated capillary column prepared for gas chromatographic (GC) separation of different types of organic compounds, including n-alkanes, n-alcohols, alkylbenzenes, isomers, especially for racemic compounds. There are 20 different kinds of racemates (e.g., alcohols, ethers, epoxides, esters, alkenes, and aldehydes) were well resolved on the FeII4L4 chiral column and a maximum resolution value for 1-phenyl-1-propanol reaches 6.17. The FeII4L4 coated column exhibited high column efficiency (3100 plates m-1 for n-dodecane) and good enantiomeric resolution complementary to that of a commercial ß-DEX 120 column and the previously reported chiral MOC [Fe4L6] (ClO4)8 coated column. The relative standard deviation (RSDs) of the peak area and retention time of glycidol and nitrotoluene were below 1.2 %. This study reveals that chiral MOCs have good application prospects in chromatographic separation.

10.
Adv Sci (Weinh) ; : e2308505, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38838052

RESUMO

With the increasing incidence of kidney diseases, there is an urgent need to develop therapeutic strategies to combat post-injury fibrosis. Immune cells, including platelets, play a pivotal role in this repair process, primarily through their released cytokines. However, the specific role of platelets in kidney injury and subsequent repair remains underexplored. Here, the detrimental role of platelets in renal recovery following ischemia/reperfusion injury and its contribution to acute kidney injury  to chronic kidney disease transition is aimed to investigated. In this study, it is shown that depleting platelets accelerates injury resolution and significantly reduces fibrosis. Employing advanced single-cell and spatial transcriptomic techniques, macrophages as the primary mediators modulated by platelet signals is identified. A novel subset of macrophages, termed "cycling M2", which exhibit an M2 phenotype combined with enhanced proliferative activity is uncovered. This subset emerges in the injured kidney during the resolution phase and is modulated by platelet-derived thrombospondin 1 (THBS1) signaling, acquiring profibrotic characteristics. Conversely, targeted inhibition of THBS1 markedly downregulates the cycling M2 macrophage, thereby mitigating fibrotic progression. Overall, this findings highlight the adverse role of platelet THBS1-boosted cycling M2 macrophages in renal injury repair and suggest platelet THBS1 as a promising therapeutic target for alleviating inflammation and kidney fibrosis.

11.
Clin Cancer Res ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869658

RESUMO

PURPOSE: This study aimed to report the five-year clinical outcomes of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell (HDS269B) therapy in relapsed/refractory multiple myeloma (RRMM) patients, including those with poor performance status (Eastern Cooperative Oncology Group [ECOG] 3-4), and to identify factors influencing long-term outcomes. METHODS: Forty-nine RRMM patients enrolled from 2016 to 2020 received HDS269B (9×106 cells/kg) after receiving a conditioning chemotherapy consisting of cyclophosphamide and fludarabine. The overall response, long-term outcomes, and safety were assessed, as were their associations with clinical and disease characteristics. RESULTS: With a median follow-up of 59.0 months, the overall response rate was 77.55%. The median progression-free survival (PFS) and overall survival (OS) were 9.5 months (95% confidence interval [CI], 5.01-13.99) and 20.0 months (95% CI, 11.26-28.74), respectively. The 5-year PFS and OS rates were 21.3% (95% CI, 12.3%-36.7%) and 34.1% (95% CI, 22.7%-51.3%), respectively. Patients with ECOG 0-2 had marked longer survival, with a median PFS of 11.0 months and median OS of 41.8 months. Early minimal residual disease negativity, and higher and persistent CAR-T cell expansion and absence of extramedullary disease were associated with better survival outcomes. No new CAR-T cell therapy associated toxicities were observed. Importantly, ECOG 0-2, prior therapy lines <4, and CAR-T cell persistence at ≥6 months were independently associated with longer OS. CONCLUSIONS: HDS269B is effective and safe, especially for patients with ECOG 0-2. Early CAR-T cell intervention may improve prognosis in patients with RRMM.

12.
PLoS Comput Biol ; 20(6): e1012193, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865380

RESUMO

Host-associated resident microbiota can protect their host from pathogens-a community-level trait called colonization resistance. The effect of the diversity of the resident community in previous studies has shown contradictory results, with higher diversity either strengthening or weakening colonization resistance. To control the confounding factors that may lead to such contradictions, we use mathematical simulations with a focus on species interactions and their impact on colonization resistance. We use a mediator-explicit model that accounts for metabolite-mediated interactions to perform in silico invasion experiments. We show that the relationship between colonization resistance and species richness of the resident community is not monotonic because it depends on two underlying trends as the richness of the resident community increases: a decrease in instances of augmentation (invader species added, without driving out resident species) and an increase in instances of displacement (invader species added, driving out some of the resident species). These trends hold consistently under different parameters, regardless of the number of compounds that mediate interactions between species or the proportion of the facilitative versus inhibitory interactions among species. Our results show a positive correlation between resistance and diversity in low-richness communities and a negative correlation in high-richness communities, offering an explanation for the seemingly contradictory trend in the resistance-diversity relationship in previous reports.

13.
BMJ Open ; 14(6): e078357, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862219

RESUMO

INTRODUCTION: The onset of cancer compels patients to grapple with existential questions. Enabling individuals with cancer, irrespective of the disease stage, to experience meaningful lives is of utmost importance in enhancing their overall quality of life. This study will synthesise qualitative research evidence to understand cancer patients' perceptions and perspectives regarding their meaning in life. Such insights ultimately contribute to enhancing the profound experience of meaning throughout the life course of cancer patients. METHODS AND ANALYSIS: The English and Chinese databases we will search include the Cochrane Library, PubMed, MEDLINE, Web of Science, EMbase, CINAHL, PsycINFO, China National Knowledge Infrastructure, Wan Fang Data, Chinese Biomedical Literature Database and VIP Database for Chinese Technical Periodicals. Two independent reviewers will assess the quality of the included studies using the standard JBI Critical Appraisal Checklist for Qualitative Research and extract data using the standard JBI Data Extraction Tool for Qualitative Research. The JBI meta-aggregation approach will be employed to compare, analyse and summarise the original results. To enhance confidence in the synthesised results of the qualitative study, the final synthesised study results will be graded using the JBI ConQual approach. ETHICS AND DISSEMINATION: External ethical approval is not necessary for this review since it involves a retrospective analysis of publicly available primary data through secondary analysis. The findings of the review will be disseminated by publishing them in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023447664.


Assuntos
Neoplasias , Pesquisa Qualitativa , Qualidade de Vida , Projetos de Pesquisa , Humanos , Neoplasias/psicologia , Metanálise como Assunto , Percepção
14.
Nat Commun ; 15(1): 3766, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704382

RESUMO

Coordination cages have been widely reported to bind a variety of guests, which are useful for chemical separation. Although the use of cages in the solid state benefits the recycling, the flexibility, dynamicity, and metal-ligand bond reversibility of solid-state cages are poor, preventing efficient guest encapsulation. Here we report a type of coordination cage-integrated solid materials that can be swelled into gel in water. The material is prepared through incorporation of an anionic FeII4L6 cage as the counterion of a cationic poly(ionic liquid) (MOC@PIL). The immobilized cages within MOC@PILs have been found to greatly affect the swelling ability of MOC@PILs and thus the mechanical properties. Importantly, upon swelling, the uptake of water provides an ideal microenvironment within the gels for the immobilized cages to dynamically move and flex that leads to excellent solution-level guest binding performances. This concept has enabled the use of MOC@PILs as efficient adsorbents for the removal of pollutants from water and for the purification of toluene and cyclohexane. Importantly, MOC@PILs can be regenerated through a deswelling strategy along with the recycling of the extracted guests.

15.
J Chem Theory Comput ; 20(9): 3766-3778, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38708859

RESUMO

Simulation of surface processes is a key part of computational chemistry that offers atomic-scale insights into mechanisms of heterogeneous catalysis, diffusion dynamics, and quantum tunneling phenomena. The most common theoretical approaches involve optimization of reaction pathways, including semiclassical tunneling pathways (called instantons). The computational effort can be demanding, especially for instanton optimizations with an ab initio electronic structure. Recently, machine learning has been applied to accelerate reaction-pathway optimization, showing great potential for a wide range of applications. However, previous methods still suffer from numerical and efficiency issues and were not designed for condensed-phase reactions. We propose an improved framework based on Gaussian process regression for general transformed coordinates, which has improved efficiency and numerical stability, and we propose a descriptor that combines internal and Cartesian coordinates suitable for modeling surface processes. We demonstrate with 11 instanton optimizations in three representative systems that the improved approach makes ab initio instanton optimization significantly cheaper, such that it becomes not much more expensive than a classical transition-state theory rate calculation.

16.
Int J Ophthalmol ; 17(5): 806-814, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766346

RESUMO

AIM: To explore the effects of hepatocyte growth factor (HGF) on retinal pigment epithelium (RPE) cell behaviors. METHODS: The human adult retinal pigment epithelial cell line-19 (ARPE-19) were treated by HGF or mesenchymal-epithelial transition factor (MET) inhibitor SU11274 in vitro. Cell viability was detected by a Cell Counting Kit-8 assay. Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay, respectively. The expression levels of MET, phosphorylated MET, protein kinase B (AKT), and phosphorylated AKT proteins were determined by Western blot assay. The MET and phosphorylated MET proteins were also determined by immunofluorescence assay. RESULTS: HGF increased ARPE-19 cells' viability, proliferation and migration, and induced an increase of phosphorylated MET and phosphorylated AKT proteins. SU11274 significantly reduced cell viability, proliferation, and migration and decreased the expression of MET and AKT proteins. SU11274 suppressed HGF-induced increase of viability, proliferation, and migration in ARPE-19 cells. Additionally, SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins. CONCLUSION: HGF enhances cellular viability, proliferation, and migration in RPE cells through the MET/AKT signaling pathway, whereas this enhancement is suppressed by the MET inhibitor SU11274. HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.

17.
Ann Med ; 56(1): 2352606, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38728617

RESUMO

BACKGROUND: Pertussis (Whooping Cough) is a respiratory infection caused by Bordetella pertussis. Pertussis usually occurs in childhood; severe infections are most common in infants. It can be fatal with severe complications such as pulmonary hypertension, heart failure, and encephalitis. OBJECTIVES: We sought to synthesize the existing literature on severe pertussis in infants and inform further study. METHODS: A scoping review was performed based on the methodological framework developed by Arksey & O'Malley. Search in Pubmed and Embase databases, with no restrictions on the language and date of publication. RESULTS: Of the 1299 articles retrieved, 64 were finally included. The selected articles were published between 1979 and 2022, with 90.6% (58/64) of the studies in the last two decades. The studies covered epidemiology, pathology, clinical characteristics, risk factors, treatments, and burden of disease. CONCLUSION: The literature reviewed suggests that studies on severe pertussis in infants covered a variety of clinical concerns. However, these studies were observational, and experimental studies are needed to provide high-quality evidence.


Assuntos
Bordetella pertussis , Coqueluche , Humanos , Coqueluche/epidemiologia , Lactente , Fatores de Risco , Índice de Gravidade de Doença , Vacina contra Coqueluche/administração & dosagem
18.
Small ; : e2312141, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801318

RESUMO

Reactive oxygen species (ROS)-mediated emerging treatments exhibit unique advantages in cancer therapy in recent years. While the efficacy of ROS-involved tumor therapy is greatly restricted by complex tumor microenvironment (TME). Herein, a dual-metal CaO2@CDs-Fe (CCF) nanosphere, with TME response and regulation capabilities, are proposed to improve ROS lethal power by a multiple cascade synergistic therapeutic strategy with domino effect. In response to weak acidic TME, CCF will decompose, accompanied with intracellular Ca2+ upregulated and abundant H2O2 and O2 produced to reverse antitherapeutic TME. Then the exposed CF cores can act as both Fenton agent and sonosensitizer to generate excessive ROS in the regulated TME for enhanced synergistic CDT/SDT. In combination with calcium overloading, the augmented ROS induced oxidative stress will cause more severe mitochondrial damage and cellular apoptosis. Furthermore, CCF can also reduce GPX4 expression and enlarge the lipid peroxidation, causing ferroptosis and apoptosis in parallel. These signals of damage will finally initiate damage-associated molecular patterns to activate immune response and to realize excellent antitumor effect. This outstanding domino ROS/calcium loading synergistic effect endows CCF with excellent anticancer effect to efficiently eliminate tumor by apoptosis/ferroptosis/ICD both in vitro and in vivo.

19.
Nanoscale ; 16(21): 10273-10282, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38717507

RESUMO

Intravesical instillation is the common therapeutic strategy for bladder cancer. Besides chemo drugs, nanoparticles are used as intravesical instillation reagents, offering appealing therapeutic approaches for bladder cancer treatment. Metal oxide nanoparticle based chemodynamic therapy (CDT) converts tumor intracellular hydrogen peroxide to ROS with cancer cell-specific toxicity, which makes it a promising approach for the intravesical instillation of bladder cancer. However, the limited penetration of nanoparticle based therapeutic agents into the mucosa layer of the bladder wall poses a great challenge for the clinical application of CDT in intravesical instillation. Herein, we developed a 1064 nm NIR-II light driven hydrogel nanomotor for the CDT for bladder cancer via intravesical instillation. The hydrogel nanomotor was synthesized via microfluidics, wrapped with a lipid bilayer, and encapsulates CuO2 nanoparticles as a CDT reagent and core-shell structured Fe3O4@Cu9S8 nanoparticles as a fuel reagent with asymmetric distribution in the nanomotor (LipGel-NM). An NIR-II light irradiation of 1064 nm drives the active motion of LipGel-NMs, thus facilitating their distribution in the bladder and deep penetration into the mucosa layer of the bladder wall. After FA-mediated endocytosis in bladder cancer cells, CuO2 is released from LipGel-NMs due to the acidic intracellular environment for CDT. The NIR-II light powered active motion of LipGel-NMs effectively enhances CDT, providing a promising strategy for bladder cancer therapy.


Assuntos
Cobre , Hidrogéis , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/terapia , Hidrogéis/química , Hidrogéis/farmacologia , Humanos , Cobre/química , Cobre/farmacologia , Linhagem Celular Tumoral , Animais , Administração Intravesical , Camundongos , Raios Infravermelhos , Feminino
20.
J Immunother ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38800996

RESUMO

RAD51, a key recombinase that catalyzes homologous recombination (HR), is commonly overexpressed in multiple cancers. It is curial for DNA damage repair (DDR) to maintain genomic integrity which could further determine the therapeutic response. Herein, we attempt to explore the clinical value of RAD51 in therapeutic guidance in muscle-invasive bladder cancer (MIBC). In this retrospective study, a total of 823 patients with MIBC were included. Zhongshan hospital (ZSHS) cohort (n=134) and The Cancer Genome Atlas-Bladder Cancer (TCGA-BLCA) cohort (n=391) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n=298) was utilized to interrogate the predictive efficacy of RAD51 status to programmed cell death ligand-1 (PD-L1) blockade. In addition, the association of RAD51 with genomic instability and tumor immune contexture was investigated. Patients with RAD51 overexpression were more likely to benefit from both platinum-based chemotherapy and immunotherapy rather than RAD51-low patients. The TMB high PD-L1 high RAD51 high subgroup possessed the best clinical benefits from PD-L1 blockade. RAD51-high tumors featured by genomic instability were correlated to highly inflamed and immunogenic contexture with activated immunotherapeutic pathway in MIBC. RAD51 could serve as a prognosticator for treatment response to platinum-based chemotherapy and PD-L1 inhibitor in MIBC patients. Besides, it could also improve the predictive efficacy of TMB and PD-L1.

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