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1.
J Org Chem ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951997

RESUMO

We have successfully synthesized a series of bidentate ligands by utilizing 2-(trimethylsilyl)phenyl trifluorosulfonate as a precursor for the benzyl group. This method proceeded by inserting a polythiourea into the C═S π-bond, intramolecular ring proton migration, and ring opening. Salient features of this strategy are mild reaction conditions, a novel product structure, excellent stereochemistry, and a good functional group tolerance. Furthermore, a series of density functional theory calculations were performed to gain insights into the transfer mechanism.

2.
mLife ; 3(2): 167-175, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38948150

RESUMO

Atherosclerosis is a chronic inflammatory metabolic disease with a complex pathogenesis. However, the exact details of its pathogenesis are still unclear, which limits effective clinical treatment of atherosclerosis. Recently, multiple studies have demonstrated that the gut microbiota plays a pivotal role in the onset and progression of atherosclerosis. This review discusses possible treatments for atherosclerosis using the gut microbiome as an intervention target and summarizes the role of the gut microbiome and its metabolites in the development of atherosclerosis. New strategies for the treatment of atherosclerosis are needed. This review provides clues for further research on the mechanisms of the relationship between the gut microbiota and atherosclerosis.

3.
Org Lett ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984739

RESUMO

Regioselective halogenation of six-membered N-heteroarenes is crucial for precise functional derivatization. We present a meta-selective halogenation method for pyridines, quinolines, and isoquinolines via electrophilic halogen radical addition utilizing an N-benzyl activation strategy. This method achieves C3- and C5-dihalogenation in pyridines, C3- and C6-dihalogenation in quinolines, and C3-monohalogenation in isoquinolines. The feasibility and potential applications of this method were validated through scale-up reactions and the bromination of quinoline derivatives with biomolecular fragments.

4.
Ecotoxicology ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39001972

RESUMO

The heavy metal cadmium (Cd) is a toxic and bioaccumulative metal that can be enriched in the tissues and organs of living organisms through the digestive tract. However, more research is needed to determine whether food-sourced Cd affects the homeostasis of host gut microflora. In this study, the snail Bradybaena ravida (Benson) was used as a model organism fed with mulberry leaves spiked with different concentrations of Cd (0, 0.052, 0.71, and 1.94 mg kg-1). By combining 16S rRNA high-throughput sequencing with biochemical characterization, it was found that there were increases in the overall microbial diversity and abundances of pathogenic bacteria such as Corynebacterium, Enterococcus, Aeromonas, and Rickettsia in the gut of B. ravida after exposure to Cd. However, the abundances of potential Cd-resistant microbes in the host's gut, including Sphingobacterium, Lactococcus, and Chryseobacterium, decreased with increasing Cd concentrations in the mulberry leaves. In addition, there was a significant reduction in activities of energy, nutrient metabolism, and antioxidant enzymes for gut microbiota of snails treated with high concentrations of Cd compared to those with low ones. These findings highlight the interaction of snail gut microbiota with Cd exposure, indicating the potential role of terrestrial animal gut microbiota in environmental monitoring through rapid recognition and response to environmental pollution.

5.
Poult Sci ; 103(9): 104006, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39002371

RESUMO

Chickens infected with FAdV-4 and FAdV-8b both exhibit hepatic lesions characterized by hemorrhagic necrosis and intranuclear inclusion body formation. However, only FAdV-4 induces pericardial effusion and acute mortality in chickens. To investigate the similarities and differences in the pathogenicity of HPS and IBH, this study intends to compare the infectivity and pathogenicity of FAdV-4 and FAdV-8b, 2 serotypes of fowl adenovirus isolated in our laboratory. The 2 viruses were respectively inoculated subcutaneously into SPF chicks at the neck. The clinical manifestations and pathological changes in these infected groups of chickens differed to some extent. Chickens infected with FAdV-4 exhibit evident depression and acute mortality, with a mortality rate of 60%; while those infected with FAdV-8b only display mild depression. Postmortem examination reveals serosanguinous effusion in the pericardial sac, spot-like hemorrhage, and focal necrosis in the liver of chickens infected with FAdV-4. Additionally, various degrees of edema are observed in organs such as the lungs, spleen, kidneys, and pancreas. In contrast, chickens infected with FAdV-8b exhibit spot-like hemorrhage and focal necrosis in the liver but do not display pericardial effusion or widespread organ edema. Histopathological examination demonstrates that both FAdV-4 and FAdV-8b can induce inflammatory reactions of varying degrees in the kidneys, pancreas, and duodenum of chickens, while reducing the necrosis of bursa of Fabricius, thymus, and spleen lymphocytes. Our data preliminarily reveal that both FAdV-4 and FAdV-8b can induce strong pathogenicity in chickens.

6.
Nano Lett ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007697

RESUMO

The technology of combining multiple emission centers to exploit white-light-emitting (WLE) materials by taking advantage of porous metal-organic frameworks (MOFs) is mature, but preparing undoped WLE MOFs remains a challenge. Herein, a pressure-treated strategy is reported to achieve efficient white photoluminescence (PL) in undoped [Zn(Tdc)(py)]n nanocrystals (NCs) at ambient conditions, where the Commission International del'Eclairage coordinates and color temperature reach (0.31, 0.37) and 6560 K, respectively. The initial [Zn(Tdc)(py)]n NCs exhibit weak-blue PL consisting of localized excited (LE) and planarized intramolecular charge transfer (PLICT) states. After pressure treatment, the emission contributions of LE and PLICT states are balanced by increasing the planarization of subunits, thereby producing white PL. Meanwhile, the reduction of nonradiative decay triggered by the planarized structure results in 5-fold PL enhancement. Phosphor-converted light-emitting diodes based on pressure-treated samples show favorable white-light characteristics. The finding provides a new platform for the development of undoped WLE MOFs.

7.
PeerJ ; 12: e17626, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948226

RESUMO

Background: Abnormal gait is prevalent among the elderly population, leading to reduced physical activity, increased risk of falls, and the potential development of dementia and disabilities, thus degrading the quality of life in later years. Numerous studies have highlighted the crucial roles of lower limb muscle strength asymmetry and static postural control in gait, and the reciprocal influence of lower limb muscle strength asymmetry on static postural control. However, research exploring the interrelationship between lower limb muscle strength asymmetry, static postural control, and gait performance has been limited. Methods: A total of 55 elderly participants aged 60 to 75 years were recruited. Isokinetic muscle strength testing was used to assess bilateral knee extension strength, and asymmetry values were calculated. Participants with asymmetry greater than 15% were categorized as the Asymmetry Group (AG), while those with asymmetry less than 15% were classified in the Symmetry Group (SG). Gait parameters were measured using a plantar pressure gait analysis system to evaluate gait performance, and static postural control was assessed through comfortable and narrow stance tests. Results: First, participants in the AG demonstrated inferior gait performance, characterized by slower gait speed, longer stance time and percentage of stance time in gait, and smaller swing time and percentage of swing time in gait. Spatial-temporal gait parameters of the weaker limb tended to be abnormal. Second, static postural control indices were higher in AG compared to SG in all aspects except for the area of ellipse during the comfortable stance with eyes open test. Third, abnormal gait parameters were associated with static postural control. Conclusion: Firstly, elderly individuals with lower limb muscle strength asymmetry are prone to abnormal gait, with the weaker limb exhibiting poorer gait performance. Secondly, lower limb muscle strength asymmetry contributes to diminished static postural control in the elderly. Thirdly, the mechanism underlying abnormal gait in the elderly due to lower limb muscle strength asymmetry may be linked to a decline in static postural control.


Assuntos
Marcha , Extremidade Inferior , Força Muscular , Equilíbrio Postural , Humanos , Idoso , Força Muscular/fisiologia , Masculino , Feminino , Equilíbrio Postural/fisiologia , Extremidade Inferior/fisiologia , Marcha/fisiologia , Pessoa de Meia-Idade
8.
Front Psychol ; 15: 1378143, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827894

RESUMO

This study conducts a bibliometric analysis using the Web of Science database on 1,950 articles published in the journal Mindfulness from 2012 to 2022. By constructing a knowledge graph, the research delineates the evolution, stages of development, and emerging trends in the field of mindfulness. Significant growth in the annual publication volume has been observed since 2012, with the research progression segmented into three distinct phases. The United States has emerged as a pivotal contributor to the field, dominating in terms of publication volume, researcher involvement, and institutional contributions. Through the application of keyword co-occurrence and reference co-citation analysis, five principal clusters were identified, focusing on mindfulness, meditation, depression, stress, and self-compassion, underscoring these as focal research areas. Furthermore, the exploration of mindfulness within the educational sphere in Taiwan is still nascent, signaling a critical need for bolstered research support in diverse thematic domains.

9.
Natl Sci Rev ; 11(7): nwae177, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38883289

RESUMO

Covalent-organic frameworks (COFs) with photoinduced donor-acceptor (D-A) radical pairs show enhanced photocatalytic activity in principle. However, achieving long-lived charge separation in COFs proves challenging due to the rapid charge recombination. Here, we develop a novel strategy by combining [6 + 4] nodes to construct zyg-type 3D COFs, first reported in COF chemistry. This structure type exhibits a fused Olympic-rings-like shape, which provides a platform for stabilizing the photoinduced D-A radical pairs. The zyg-type COFs containing catalytically active moieties such as triphenylamine and phenothiazine (PTZ) show superior photocatalytic production rates of hydrogen peroxide (H2O2). Significantly, the photochromic radical states of these COFs show up to 400% enhancement in photocatalytic activity compared to the parent states, achieving a remarkable H2O2 synthesis rate of 3324 µmol g-1 h-1, which makes the PTZ-COF one of the best crystalline porous photocatalysts in H2O2 production. This work will shed light on the synthesis of efficient 3D COF photocatalysts built on topologies that can facilitate photogenerating D-A radical pairs for enhanced photocatalysis.

10.
JCI Insight ; 9(12)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38912585

RESUMO

The diffuse axonal damage in white matter and neuronal loss, along with excessive neuroinflammation, hinder long-term functional recovery after traumatic brain injury (TBI). MicroRNAs (miRs) are small noncoding RNAs that negatively regulate protein-coding target genes in a posttranscriptional manner. Recent studies have shown that loss of function of the miR-15a/16-1 cluster reduced neurovascular damage and improved functional recovery in ischemic stroke and vascular dementia. However, the role of the miR-15a/16-1 cluster in neurotrauma is poorly explored. Here, we report that genetic deletion of the miR-15a/16-1 cluster facilitated the recovery of sensorimotor and cognitive functions, alleviated white matter/gray matter lesions, reduced cerebral glial cell activation, and inhibited infiltration of peripheral blood immune cells to brain parenchyma in a murine model of TBI when compared with WT controls. Moreover, intranasal delivery of the miR-15a/16-1 antagomir provided similar brain-protective effects conferred by genetic deletion of the miR-15a/16-1 cluster after experimental TBI, as evidenced by showing improved sensorimotor and cognitive outcomes, better white/gray matter integrity, and less inflammatory responses than the control antagomir-treated mice after brain trauma. miR-15a/16-1 genetic deficiency and miR-15a/16-1 antagomir also significantly suppressed inflammatory mediators in posttrauma brains. These results suggest miR-15a/16-1 as a potential therapeutic target for TBI.


Assuntos
Lesões Encefálicas Traumáticas , Modelos Animais de Doenças , MicroRNAs , Recuperação de Função Fisiológica , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/genética , Camundongos , Masculino , Camundongos Knockout , Camundongos Endogâmicos C57BL , Encéfalo/patologia , Encéfalo/metabolismo
11.
Microbes Infect ; : 105381, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914369

RESUMO

BACKGROUND: In both lung adenocarcinoma (LUAD) and severe acute respiratory syndrome (SARS), uncontrolled inflammation can be detected in lung tissue. The PDZ-binding motif (PBM) in the SARS-CoV-1 E protein has been demonstrated to be a virulence factor that induces a cytokine storm. METHODS: To identify gene expression fluctuations induced by PBM, microarray sequencing data of lung tissue infected with wild-type (SARS-CoV-1-E-wt) or recombinant virus (SARS-CoV-1-E-mutPBM) were analyzed, followed by functional enrichment analysis. To understand the role of the screened genes in LUAD, overall survival and immune correlation were calculated. RESULTS: A total of 12 genes might participate in the initial and developmental stages of LUAD through expression variation and mutation. Moreover, dysregulation of a total of 12 genes could lead to a poorer prognosis. In addition, the downregulation of MAMDC2 and ITGA8 by PBM could also affect patient prognosis. Although the conserved PBM (-D-L-L-V-) can be found at the end of the carboxyl terminus in multiple E proteins of coronaviruses, the specific function of each protein depends on the entire amino acid sequence. CONCLUSIONS: In summary, PBM containing the SARS-CoV-1 E protein promoted the carcinogenesis of LUAD by dysregulating important gene expression profiles and subsequently influencing the immune response and overall prognosis.

12.
Nat Commun ; 15(1): 5017, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866776

RESUMO

Ultra-low temperature resistant adhesive is highly desired yet scarce for material adhesion for the potential usage in Arctic/Antarctic or outer space exploration. Here we develop a solvent-free processed low-temperature tolerant adhesive with excellent adhesion strength and organic solvent stability, wide tolerable temperature range (i.e. -196 to 55 °C), long-lasting adhesion effect ( > 60 days, -196 °C) that exceeds the classic commercial hot melt adhesives. Furthermore, combine experimental results with theoretical calculations, the strong interaction energy between polyoxometalate and polymer is the main factor for the low-temperature tolerant adhesive, possessing enhanced cohesion strength, suppressed polymer crystallization and volumetric contraction. Notably, manufacturing at scale can be easily achieved by the facile scale-up solvent-free processing, showing much potential towards practical application in Arctic/Antarctic or planetary exploration.

13.
Acta Pharmacol Sin ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811775

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor precursor homologous domain A (EGF-A) of low-density lipoprotein receptor (LDLR) in the liver and triggers the degradation of LDLR via the lysosomal pathway, consequently leading to an elevation in plasma LDL-C levels. Inhibiting PCSK9 prolongs the lifespan of LDLR and maintains cholesterol homeostasis in the body. Thus, PCSK9 is an innovative pharmacological target for treating hypercholesterolemia and atherosclerosis. In this study, we discovered that E28362 was a novel small-molecule PCSK9 inhibitor by conducting a virtual screening of a library containing 40,000 compounds. E28362 (5, 10, 20 µM) dose-dependently increased the protein levels of LDLR in both total protein and the membrane fraction in both HepG2 and AML12 cells, and enhanced the uptake of DiI-LDL in AML12 cells. MTT assay showed that E28362 up to 80 µM had no obvious toxicity in HepG2, AML12, and HEK293a cells. The effects of E28362 on hyperlipidemia and atherosclerosis were evaluated in three different animal models. In high-fat diet-fed golden hamsters, administration of E28362 (6.7, 20, 60 mg·kg-1·d-1, i.g.) for 4 weeks significantly reduced plasma total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and PCSK9 levels, and reduced liver TC and TG contents. In Western diet-fed ApoE-/- mice (20, 60 mg·kg-1·d-1, i.g.) and human PCSK9 D374Y overexpression mice (60 mg·kg-1·d-1, i.g.), administration of E28362 for 12 weeks significantly decreased plasma LDL-C levels and the area of atherosclerotic lesions in en face aortas and aortic roots. Moreover, E28362 significantly increased the protein expression level of LDLR in the liver. We revealed that E28362 selectively bound to PCSK9 in HepG2 and AML12 cells, blocked the interaction between LDLR and PCSK9, and induced the degradation of PCSK9 through the ubiquitin-proteasome pathway, which finally resulted in increased LDLR protein levels. In conclusion, E28362 can block the interaction between PCSK9 and LDLR, induce the degradation of PCSK9, increase LDLR protein levels, and alleviate hyperlipidemia and atherosclerosis in three distinct animal models, suggesting that E28362 is a promising lead compound for the treatment of hyperlipidemia and atherosclerosis.

14.
BMC Plant Biol ; 24(1): 433, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773359

RESUMO

BACKGROUND: Freezing stress is one of the major abiotic stresses that causes extensive damage to plants. LEA (Late embryogenesis abundant) proteins play a crucial role in plant growth, development, and abiotic stress. However, there is limited research on the function of LEA genes in low-temperature stress in Brassica napus (rapeseed). RESULTS: Total 306 potential LEA genes were identified in B. rapa (79), B. oleracea (79) and B. napus (148) and divided into eight subgroups. LEA genes of the same subgroup had similar gene structures and predicted subcellular locations. Cis-regulatory elements analysis showed that the promoters of BnaLEA genes rich in cis-regulatory elements related to various abiotic stresses. Additionally, RNA-seq and real-time PCR results indicated that the majority of BnaLEA family members were highly expressed in senescent tissues of rapeseed, especially during late stages of seed maturation, and most BnaLEA genes can be induced by salt and osmotic stress. Interestingly, the BnaA.LEA6.a and BnaC.LEA6.a genes were highly expressed across different vegetative and reproductive organs during different development stages, and showed strong responses to salt, osmotic, and cold stress, particularly freezing stress. Further analysis showed that overexpression of BnaA.LEA6.a increased the freezing tolerance in rapeseed, as evidenced by lower relative electrical leakage and higher survival rates compared to the wild-type (WT) under freezing treatment. CONCLUSION: This study is of great significance for understanding the functions of BnaLEA genes in freezing tolerance in rapeseed and offers an ideal candidate gene (BnaA.LEA6.a) for molecular breeding of freezing-tolerant rapeseed cultivars.


Assuntos
Brassica napus , Congelamento , Proteínas de Plantas , Brassica napus/genética , Brassica napus/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Família Multigênica , Genoma de Planta , Resposta ao Choque Frio/genética
15.
Eur J Med Res ; 29(1): 277, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725045

RESUMO

BACKGROUND: Metabolic disorders (MetDs) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetDs and pulmonary tuberculosis (PTB) remains poorly understood. METHOD: Summary statistics for exposure and outcomes from genome-wide association studies (GWASs) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene-exposure dataset. The 14 clinical factors were categorized into three groups: metabolic laboratory markers, blood pressure, and the MetS diagnostic factors. The causal relationship between metabolic factors and PTB were analyzed using two-sample Mendelian Randomization (MR). Additionally, the direct effects on the risk of PTB were investigated through multivariable MR. The primary method employed was the inverse variance-weighted (IVW) model. The sensitivity of this MR analysis was evaluated using MR-Egger regression and the MR-PRESSO global test. RESULTS: According to the two-sample MR, HDL-C, HbA1c, TP, and DM were positively correlated with the incidence of active TB. According to the multivariable MR, HDL-C (IVW: OR 2.798, 95% CI 1.484-5.274, P = 0.001), LDL (IVW: OR 4.027, 95% CI 1.140-14.219, P = 0.03) and TG (IVW: OR 2.548, 95% CI 1.269-5.115, P = 0.009) were positively correlated with the occurrence of PTB. TC (OR 0.131, 95% CI 0.028-0.607, P = 0.009) was negatively correlated with the occurrence of PTB. We selected BMI, DM, HDL-C, SBP, and TG as the diagnostic factors for metabolic syndrome. DM (IVW, OR 1.219, 95% CI 1.040-1.429 P = 0.014) and HDL-C (IVW, OR 1.380, 95% CI 1.035-1.841, P = 0.028) were directly correlated with the occurrence of PTB. CONCLUSIONS: This MR study demonstrated that metabolic disorders, mainly hyperglycemia, and dyslipidemia, are associated with the incidence of active pulmonary tuberculosis.


Assuntos
Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Doenças Metabólicas , Tuberculose Pulmonar , Humanos , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/sangue , Doenças Metabólicas/genética , Doenças Metabólicas/epidemiologia , Fatores de Risco
16.
Int J Cancer ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783579

RESUMO

The C677T polymorphism in the MTHFR gene and its role in folate metabolism, impacting serum folate metabolites like THF and 5-MTHF, is a critical but underexplored area in cancer research. This nested case-control study utilized data from CHHRS, involving 87,492 hypertensive adults without prior cancer. During a median of 2.02 years, we identified 1332 cancer cases and matched controls based on age, sex, and residency. Serum levels of folate, THF, and 5-MTHF were measured, and the MTHFR C677T gene polymorphism was considered. Statistical analyses included restricted cubic spline regression and conditional logistic regression models. Serum THF levels were inversely associated with overall cancer risk (ORper SD = 0.90, 95% CI = 0.82-0.99), while 5-MTHF levels showed a negative association in the general cohort (ORQ3 vs. Q1 = 0.76, 95% CI = 0.60-0.96; ORQ4 vs. Q1 = 0.75, 95% CI = 0.58-0.98) and in individuals with MTHFR C677T (CC + CT) polymorphism (ORper SD = 0.87, 95% CI = 0.77-0.99; ORQ4 VS. Q1 = 0.79, 95% CI = 0.61-0.98), but a positive association in the MTHFR C677T (TT) subgroup (ORper SD = 1.89, 95% CI = 1.02-3.72; ORQ4 VS. Q1 = 2.17, 95% CI = 1.06-8.21). The impact of folate, THF, and 5-MTHF on cancer risk varied significantly across different cancer types and MTHFR C677T genotypes. This study provides novel insights into the variable effects of folate and its metabolites on cancer risk, influenced by genetic factors like the MTHFR C677T polymorphism and cancer type.

17.
Microb Pathog ; 192: 106703, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38763315

RESUMO

Streptococcus equissp.zooepidemicus (SEZ) is a crucial pathogen and contributes to various infections in numerous animal species. Swine streptococcicosis outbreak caused by SEZ has been reported in several countries in recent years. SzM protein is a cell membrane-anchored protein, which exhibits as an important virulence factor of SEZ. Effects of SzM protein on host innate immune need further study. Here, recombinant SzM (rSzM) protein of the SEZ was obtained, and mice were intraperitoneally injected with rSzM protein. We discovered that rSzM protein can recruit neutrophils into the injected site. In further study, neutrophils were isolated and treated with rSzM protein, NETs release were triggered by rSzM protein independently, and GSDMD protein was promoted-expressed and activated. In order to investigate the role of GSDMD in NETs formation, neutrophils isolated from WT mice and GSDMD-/- mice were treated with rSzM protein. The results showed that GSDMD deficiency suppressed the NETs release. In conclusion, SzM protein of SEZ can trigger the NETs release in a GSDMD-depending manner.


Assuntos
Proteínas de Bactérias , Armadilhas Extracelulares , Neutrófilos , Infecções Estreptocócicas , Streptococcus equi , Fatores de Virulência , Animais , Camundongos , Neutrófilos/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/imunologia , Streptococcus equi/genética , Streptococcus equi/imunologia , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Camundongos Knockout , Proteínas Recombinantes/genética , Imunidade Inata , Camundongos Endogâmicos C57BL , Gasderminas , Proteínas de Ligação a Fosfato
18.
Cancer Lett ; 594: 216992, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38797231

RESUMO

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive cancer with an extremely poor prognosis, and new treatment options are needed. Recently, immunotherapy has emerged as an efficient treatment against malignant tumors, but less effective in iCCA. Activation of stimulator of interferon genes (STING) signaling could reignite immunologically inert tumors, but the expression and role of STING in iCCA remains to be determined. Here, we show STING is expressed in iCCA, and patients with high expression of STING in early-stage iCCA have a longer overall survival than those have low expression. Increased immune cell infiltration in early-stage iCCA corresponds to elevated STING expression. In mice iCCA models, treatment with the STING agonist MSA-2 show stage-specific inhibitory effects on tumors, with beneficial effects in early-stage tumors but not with advanced-stage cancer. This discrepancy was associated with greater programmed cell death ligand 1 (PD-L1) expression in advanced-stage tumors. Combination therapy targeting PD-L1 and MSA-2 strikingly reduced tumor burden in such tumors compared to either monotherapy. Cumulatively, these data demonstrate that STING agonism monotherapy improves the immune landscape of the tumor microenvironment in early-stage iCCA, while combination therapy ameliorates advanced-stage iCCA.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Proteínas de Membrana , Colangiocarcinoma/imunologia , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Colangiocarcinoma/tratamento farmacológico , Animais , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/agonistas , Humanos , Camundongos , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/imunologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Estadiamento de Neoplasias , Linhagem Celular Tumoral , Microambiente Tumoral/imunologia , Masculino , Feminino , Transdução de Sinais
19.
J Org Chem ; 89(11): 7741-7746, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38741558

RESUMO

A novel three-component cyclization carbonylation reaction of iodoarene-tethered propargyl ethers with amine and CO is reported. This palladium-catalyzed cascade reaction undergoes a sequence of oxidative addition, unsaturated bond migration, carbonyl insertion, and nucleophilic attack to deliver the benzofuran skeleton. Both aromatic amines and aliphatic amines could proceed smoothly in this transformation under one atm of CO.

20.
Poult Sci ; 103(7): 103840, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38772093

RESUMO

Marek's disease virus (MDV) is a significant tumorigenic virus that causes severe immunosuppression in chickens. Lentinan (LNT) is an immunomodulator containing ß-glucans and is widely used in areas such as antiviral, anticancer, and immune regulation. To investigate the immunomodulatory effects of LNT on specific pathogen-free (SPF) chicks and its potential to inhibit MDV infection, we conducted an MDV challenge experiment and observed the immune-enhancing effect of LNT on SPF chicks. The results showed that LNT promoted the growth and development of SPF chicks and induced the upregulation of cytokines such as Mx protein, interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2). The specific gravity of CD4+ T-lymphocytes and CD8+ T-lymphocytes and their ratios were also significantly upregulated. Prophylactic use of LNT inhibited MDV replication in lymphocytes, liver, and spleen. It also alleviated MDV-induced weight loss and hepatosplenomegaly in SPF chicks. The present study confirms that LNT can enhance the levels of innate and cellular immunity in SPF chicks and contributes to the inhibition of MDV replication in vivo and mitigation of immune organ damage in chicks due to MDV infection. This provides an adjunctive measure for better control of MDV infection.


Assuntos
Galinhas , Herpesvirus Galináceo 2 , Lentinano , Doença de Marek , Doenças das Aves Domésticas , Animais , Doença de Marek/imunologia , Lentinano/farmacologia , Lentinano/administração & dosagem , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/tratamento farmacológico , Herpesvirus Galináceo 2/fisiologia , Organismos Livres de Patógenos Específicos , Ração Animal/análise , Fatores Imunológicos/farmacologia , Fatores Imunológicos/administração & dosagem , Dieta/veterinária , Distribuição Aleatória
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