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1.
World J Gastrointest Oncol ; 16(6): 2271-2283, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38994170

RESUMO

The morbidity and mortality of gastrointestinal (GI) malignancies are among the highest in the world, posing a serious threat to human health. Because of the insidious onset of the cancer, it is difficult for patients to be diagnosed at an early stage, and it rapidly progresses to an advanced stage, resulting in poor treatment and prognosis. Fusobacterium nucleatum (F. nucleatum) is a gram-negative, spore-free anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal, esophageal, gastric, and pancreatic cancers via various intricate mechanisms. Recent development in novel research suggests that F. nucleatum may function as a biomarker in GI malignancies. Detecting the abundance of F. nucleatum in stool, saliva, and serum samples of patients may aid in the diagnosis, risk assessment, and prognosis monitoring of GI malignancies. This editorial systematically describes the biological roles and mechanisms of F. nucleatum in GI malignancies focusing on the application of F. nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F. nucleatum and GI tumors-related research.

2.
Adv Healthc Mater ; : e2401406, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007245

RESUMO

Tissue engineering for penile corpora cavernosa defects requires microvascular system reconstruction.GelMA hydrogels show promise for tissue regeneration. However, using stem cells faces challenges such as immune rejection, limited proliferation and differentiation, and biosafety concerns. Therefore, acellular tissue regeneration may avoid these issues. Exosomes are used from muscle-derived stem cells (MDSCs) to modify 3D-printed hydrogel scaffolds for acellular tissue regeneration. Hypoxia-preconditioned MDSC-derived exosomes are obtained to enhance the therapeutic effect. In contrast to normoxic exosomes (N-Exos), hypoxic exosomes (H-Exos) are found to markedly enhance the proliferation, migration, and capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). High-throughput sequencing analysis of miRNAs isolated from both N-Exos and H-Exos revealed a significant upregulation of miR-21-5p in H-Exos following hypoxic preconditioning. Further validation demonstrated that the miR-21-5p/PDCD4 pathway promoted the proliferation of HUVECs. Epigallocatechin gallate (EGCG) is introduced to improve the mechanical properties and biocompatibility of GelMA hydrogels. EGCG-GelMA scaffolds loaded with different types of Exos are transplanted to repair rabbit penile corpora cavernosa defects, observed the blood flow and repair status of the defect site through color Doppler ultrasound and magnetic resonance imaging, and ultimately restored the rabbit penile erection function and successfully bred offspring. Thus, acellular hydrogel scaffolds offer an effective treatment for penile corpora cavernosa defects.

3.
J Med Virol ; 96(7): e29776, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38953430

RESUMO

The genetic diversity of killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral pathogens. This study aims to explore the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL2 and HLA-A genes on hepatitis C virus (HCV) infection. A total of 2251 individuals were included in the case-control study. SNPs including KIR3DL2 rs11672983, rs3745902, rs1654644, and HLA-A rs3869062, rs12202296 were genotyped. By controlling various confounding factors using a modified logistic regression model, as well as incorporating stratified analysis, joint effects analysis, and multidimensional bioinformatics analysis, we analyzed the relationship between SNPs and HCV infection. The logistic regression analysis showed a correlation between KIR3DL2 rs11672983 AA, KIR3DL2 rs3745902 TT, and increased HCV susceptibility (p < 0.01). Stratified analysis indicated that KIR3DL2 rs1654644 and HLA-A rs3869062 also heightened HCV susceptibility in certain subgroups. A linear trend of rising HCV infection rates was observed when combining KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT (ptrend = 0.007). Bioinformatics analysis suggested these SNPs' regulatory potential and their role in altering messenger RNA secondary structure, implying their functional relevance in HCV susceptibility. Our findings indicate that KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT are significantly associated with increased susceptibility to HCV infection.


Assuntos
Predisposição Genética para Doença , Genótipo , Hepatite C , Polimorfismo de Nucleotídeo Único , Humanos , Masculino , Feminino , Estudos de Casos e Controles , Hepatite C/genética , Hepatite C/virologia , Hepatite C/imunologia , Pessoa de Meia-Idade , Adulto , Antígenos HLA-A/genética , Hepacivirus/genética , Hepacivirus/imunologia , Receptores KIR/genética , Idoso , Receptores KIR3DL2/genética
4.
Nat Commun ; 15(1): 5985, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39013850

RESUMO

The mechanism by which aging induces aortic aneurysm and dissection (AAD) remains unclear. A total of 430 participants were recruited for the screening of differentially expressed plasma microRNAs (miRNAs). We found that miR-1204 is significantly increased in both the plasma and aorta of elder patients with AAD and is positively correlated with age. Cell senescence induces the expression of miR-1204 through p53 interaction with plasmacytoma variant translocation 1, and miR-1204 induces vascular smooth muscle cell (VSMC) senescence to form a positive feedback loop. Furthermore, miR-1204 aggravates angiotensin II-induced AAD formation, and inhibition of miR-1204 attenuates ß-aminopropionitrile monofumarate-induced AAD development in mice. Mechanistically, miR-1204 directly targets myosin light chain kinase (MYLK), leading to the acquisition of a senescence-associated secretory phenotype (SASP) by VSMCs and loss of their contractile phenotype. MYLK overexpression reverses miR-1204-induced VSMC senescence, SASP and contractile phenotypic changes, and the decrease of transforming growth factor-ß signaling pathway. Our findings suggest that aging aggravates AAD via the miR-1204-MYLK signaling axis.


Assuntos
Envelhecimento , Aneurisma Aórtico , Dissecção Aórtica , Senescência Celular , MicroRNAs , Músculo Liso Vascular , Quinase de Cadeia Leve de Miosina , Transdução de Sinais , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Camundongos , Quinase de Cadeia Leve de Miosina/metabolismo , Quinase de Cadeia Leve de Miosina/genética , Envelhecimento/genética , Envelhecimento/metabolismo , Masculino , Humanos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Dissecção Aórtica/metabolismo , Dissecção Aórtica/genética , Dissecção Aórtica/patologia , Aneurisma Aórtico/metabolismo , Aneurisma Aórtico/genética , Aneurisma Aórtico/patologia , Miócitos de Músculo Liso/metabolismo , Camundongos Endogâmicos C57BL , Feminino , Fator de Crescimento Transformador beta/metabolismo , Modelos Animais de Doenças , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Angiotensina II/metabolismo , Proteínas de Ligação ao Cálcio
5.
Front Plant Sci ; 15: 1358924, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38831907

RESUMO

Introduction: Touch by neighboring plants is a common but overlooked environmental variable for plants, especially in dense vegetation. In addition, shade is inevitable for understory plants. The growth performance of clonal plant to the interaction between thigmomorphogenesis and shade response, and their impact on light adaptability is still unknown. Methods: At the present study, parental ramets of Glechoma longituba were exposed to two conditions (neighboring touch and shade), and their offspring ramets were in ambient or shaded environment. The phenotype and growth of parental and offspring ramets were analyzed. Results: The results showed that neighboring touch of parental ramets regulated the performance of offspring ramets, while the effect depended on the light environment. The parental neighboring touch occurring in ambient environment suppressed the expansion of leaf organ, showed as a shorter petiole and smaller leaf area. Moreover, G. longituba exhibited both shade avoidance and shade tolerance characters to shaded environment, such as increased leaf area ratio and leaf mass ratio, longer specific petiole length and specific stolon length. It was notable that these characters of shade response could be promoted by parental neighboring touch to some extent. Additionally, parental light environment plays an important role in offspring growth, parent with ambient light always had well-grown offspring whatever the light condition of offspring, but the growth of offspring whose parent in shaded environment was inhibited. Finally, for the offspring with shaded environment, the touch between parental ramets in shade environment showed a disadvantage on their growth, but the influence of the touch between parental ramets in ambient environment was slight. Discussion: Overall, the interaction of parental neighboring touch and shade environment complicate the growth of understory plants, the performance of plants is the integrated effect of both. These findings are conducive to an in-depth understanding of the environmental adaptation of plants.

6.
J Agric Food Chem ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833376

RESUMO

This study found that, after microwave treatment at 560 W for 30 s, alkaline protease enzymolysis significantly reduced the allergenicity of ovalbumin (OVA). Furthermore, specific adsorption of allergenic anti-enzyme hydrolyzed peptides in the enzymatic products by immunoglobulin G (IgG) bound to magnetic bead further decreased the allergenicity of OVA. The results indicated that microwave treatment disrupts the structure of OVA, increasing the accessibility of OVA to the alkaline protease. A comparison between 17 IgG-binding epitopes identified through high-performance liquid chromatography-higher energy collisional dissociation-tandem mass spectrometry and previously reported immunoglobulin E (IgE)-binding epitopes revealed a complete overlap in binding epitopes at amino acids (AA)125-135, AA151-158, AA357-366, and AA373-381. Additionally, partial overlap was observed at positions AA41-59, AA243-252, and AA320-340. Consequently, these binding epitopes were likely pivotal in eliciting the allergic reaction to OVA, warranting specific attention in future studies. In conclusion, microwave-assisted enzymolysis synergized with magnetic bead adsorption provides an effective method to reduce the allergenicity of OVA.

7.
Brain Behav ; 14(7): e3610, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38945806

RESUMO

INTRODUCTION: Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane-induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO-induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO. METHODS: Pregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00-18:00 h) during GD15-21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti-inflammatory markers and synaptic function-related proteins were assessed using molecular biology methods. RESULTS: The results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha and a reduction in the hippocampal levels of IL-10, synaptophysin, post-synaptic density-95, growth-associated protein-43, and brain-derived neurotrophic factor. CONCLUSION: Our findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.


Assuntos
Anestésicos Inalatórios , Disfunção Cognitiva , Hipocampo , Isoflurano , Doenças Neuroinflamatórias , Efeitos Tardios da Exposição Pré-Natal , Privação do Sono , Animais , Isoflurano/efeitos adversos , Isoflurano/farmacologia , Isoflurano/administração & dosagem , Feminino , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/fisiopatologia , Gravidez , Privação do Sono/complicações , Privação do Sono/fisiopatologia , Camundongos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Anestésicos Inalatórios/efeitos adversos , Anestésicos Inalatórios/farmacologia , Anestésicos Inalatórios/administração & dosagem , Sinapses/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Privação Materna , Fator Neurotrófico Derivado do Encéfalo/metabolismo
8.
Ecol Evol ; 14(6): e11525, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38932945

RESUMO

Invasive plants exert significant ecological impacts on native plants, communities, and ecosystems. However, consistent conclusions regarding how traits of invasive plants, native plants, and their divergences affect invasion dynamics are still lacking. Here, we conducted a pairwise common garden experiment to investigate how invasion was influenced not only by invasive plants but also by native plants, aiming to elucidate the role of invasive-plant traits, native-plant traits, and their divergences in invasion processes. Our findings revealed variations in invasive stage depending on the combinations of invasive and native plants. Specifically, native plants such as A. argyi, A. lavandulifolia, and C. album exhibited competitive superiority when co-occurring with the three invasive plants. S. viridis, A. vestita, and A. annua had competitive superiority when they co-occurred with E. canadensis, G. quadriradiata, and E. annuus respectively. Furthermore, our results demonstrated that the competitive abilities of invasive plants were primarily influenced by factors such as height, diameter, and biomass allocation, while native plants' competitive abilities were mainly affected by diameter, biomass allocation, and function group differences. Moreover, our analysis revealed that invasive-plant traits, native-plant traits, their divergences, and their interactions together explained 36.88% of the variation in invasion dynamics, with invasive-plant traits and the native-plant traits explaining 10.19% and 6.88%, respectively. In conclusion, the traits of invasive and native plants, along with their divergences, significantly influence interspecific relationships, and influencing the invasive stages. Divergences in competitive strategies between the native plants and invasive plants facilitated invasion processes. Our study not only contributes to understanding the mechanisms underlying invasion, but also provides a scientific foundation for predicting and managing the negative effects of invasive plants.

9.
Pestic Biochem Physiol ; 202: 105915, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879296

RESUMO

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling is activated by infections of bacteria, fungi, viruses and parasites and mediated cellular and humoral immune responses. In the pea aphid Acyrthosiphon pisum little is known about the function of JAK/STAT signaling in its immune system. In this study, we first showed that expression of genes in the JAK/STAT signaling, including the receptors Domeless1/2, Janus kinase (JAK) and transcriptional factor Stat92E, is up-regulated upon bacteria Escherichia coli and Staphylococcus aureus and fungus Beauveria bassiana infections. After knockdown of expression of these genes by means of dsRNA injection, the aphids harbored more bacteria and suffered more death after infected with E. coli and S. aureus, but showed no significant change after B. bassiana infection. Our study suggests the JAK/STAT signaling contributes to the defense against bacterial infection in the pea aphid.


Assuntos
Afídeos , Janus Quinases , Fatores de Transcrição STAT , Transdução de Sinais , Animais , Janus Quinases/metabolismo , Fatores de Transcrição STAT/metabolismo , Staphylococcus aureus/fisiologia , Escherichia coli , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Beauveria/fisiologia
10.
Toxicol Lett ; 398: 69-81, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38909920

RESUMO

Sodium para-aminosalicylic acid (PAS-Na) treatment for manganese (Mn) intoxication has shown efficacy in experimental and clinical studies, giving rise to additional studies on its efficacy for lead (Pb) neurotoxicity and its associated mechanisms of neuroprotection. The difference between PAS-Na and other metal complexing agents, such as edetate calcium sodium (CaNa2-EDTA), is firstly that PAS-Na can readily pass through the blood-brain barrier (BBB), and complex and facilitate the excretion of manganese and lead. Secondly, PAS-Na has anti-inflammatory effects. Recent studies have broadened the understanding on the mechanisms associated with efficacy of PAS-Na. The latter has been shown to modulate multifarious manganese- and lead- induced neurotoxicity, via its anti-apoptotic and anti-inflammatory effects, as well as its ability to inhibit pyroptosis, and regulate abnormal autophagic processes. These observations provide novel scientific bases and new concepts for the treatment of lead, mercury, copper, thallium, as well as other toxic encephalopathies, and implicate PAS-Na as a compound with greater prospects for clinical medical application.


Assuntos
Ácido Aminossalicílico , Intoxicação por Chumbo , Intoxicação por Manganês , Humanos , Animais , Ácido Aminossalicílico/uso terapêutico , Intoxicação por Manganês/tratamento farmacológico , Intoxicação por Chumbo/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Manganês/toxicidade
11.
Langmuir ; 40(22): 11401-11410, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38767862

RESUMO

To functionalize interfaces with supported biomembranes and membrane proteins, the challenge is to build stabilized and supported systems that mimic the native lipid microenvironment. Our objective is to control substrate-to-biomembrane spacing and the tethering chemistry so proteoliposomes can be fused and conjugated without perturbation of membrane protein function. Furthermore, the substrates need to exhibit low protein and antibody nonspecific binding to use these systems in assays. We have employed protein orthogonal coupling schemes in concert with multiarm poly(ethylene glycol) (PEG) technology to build supported biomembranes on microspheres. The lipid bilayer structures and tailored substrates of the microsphere-supported biomembranes were analyzed via flow cytometry, confocal fluorescence, and super-resolution imaging microscopy, and the lateral fluidity was quantified using fluorescence recovery after photobleaching (FRAP) techniques. Under these conditions, the 4-arm-PEG20,000-NH2 based configuration gave the most desirable tethering system based on lateral diffusivity and coverage.


Assuntos
Bicamadas Lipídicas , Polietilenoglicóis , Polietilenoglicóis/química , Bicamadas Lipídicas/química , Microesferas , Recuperação de Fluorescência Após Fotodegradação , Polímeros/química
12.
Basic Clin Pharmacol Toxicol ; 135(1): 81-97, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38780039

RESUMO

We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para-aminosalicylate (PAS-Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage. Y-maze novelty test and balance beam test were used to evaluate the motor and cognitive function of rats. Haematoxylin and eosin (H&E) and Nissl staining were performed to observe the cortical damage of rats. The results showed that the combined exposure of Mn and Fe in rats led to a synergistic effect, attenuating growth and development, and altering learning and memory as well as motor function. The combination of Mn and Fe also caused damage to the synaptic structure of PC12 cells, which is manifested as swelling of dendrites and axon terminals, and even lead to cell death. PAS-Na displayed some antagonistic effects against the Mn- and Fe-induced synaptic structural damage, growth, learning and memory impairment.


Assuntos
Ácido Aminossalicílico , Manganês , Sinapses , Animais , Ratos , Células PC12 , Sinapses/efeitos dos fármacos , Masculino , Ácido Aminossalicílico/farmacologia , Manganês/toxicidade , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Córtex Cerebral/metabolismo , Ratos Sprague-Dawley , Ferro/metabolismo , Fármacos Neuroprotetores/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Síndromes Neurotóxicas/prevenção & controle , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/patologia , Modelos Animais de Doenças
13.
Int Immunopharmacol ; 134: 112202, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38723371

RESUMO

Intervertebral disc (IVD) degeneration, induced by aging and irregular mechanical strain, is highly prevalent in the elderly population, serving as a leading cause of chronic low back pain and disability. Evolving evidence has revealed the involvement of nucleus pulposus (NP) pyroptosis in the pathogenesis of IVD degeneration, while the precise regulatory mechanisms of NP pyroptosis remain obscure. Misshapen/Nck-interacting kinase (NIK)-related kinase 1 (MINK1), a serine-threonine protein kinase, has the potential to modulate the activation of NLRP3 inflammasome, indicating its pivotal role in governing pyroptosis. In this study, to assess the significance of MINK1 in NP pyroptosis and IVD degeneration, NP tissues from patients with varying degrees of IVD degeneration, and IVD tissues from both aging-induced and lumbar spine instability (LSI) surgery-induced IVD degeneration mouse models, with or without MINK1 ablation, were meticulously evaluated. Our findings indicated a notable decline in MINK1 expression in NP tissues of patients with IVD degeneration and both mouse models as degeneration progresses, accompanied by heightened matrix degradation and increased NP pyroptosis. Moreover, MINK1 ablation led to substantial activation of NP pyroptosis in both mouse models, and accelerating ECM degradation and intensifying the degeneration phenotype in mechanically stress-induced mice. Mechanistically, MINK1 deficiency triggered NF-κB signaling in NP tissues. Overall, our data illustrate an inverse correlation between MINK1 expression and severity of IVD degeneration, and the absence of MINK1 stimulates NP pyroptosis, exacerbating IVD degeneration by activating NF-κB signaling, highlighting a potential innovative therapeutic target in treating IVD degeneration.


Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Piroptose , Adulto , Idoso , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Animais de Doenças , Degeneração do Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Núcleo Pulposo/patologia , Núcleo Pulposo/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética
14.
J Infect ; 89(1): 106181, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38744376

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with high fatality rates. The blockade of pro-inflammatory cytokines presents a promising therapeutic strategy. METHODS: We conducted a randomized clinical trial at the 154th hospital, Xinyang, Henan Province. Eligible patients with severe SFTS disease were randomly assigned in a 1:2 ratio to receive either a single intravenous infusion of tocilizumab plus usual care; or usual care only. The primary outcome was the clinical status of death/survival at day 14, while secondary outcomes included improvement from baseline in liver and kidney damage and time required for hospital discharge. The efficacy of tocilizumab plus corticosteroid was compared to those receiving corticosteroid alone. The trial is registered with the Chinese Clinical Trial Registry website (ChiCTR2300076317). RESULTS: 63 eligible patients were assigned to the tocilizumab group and 126 to the control group. The addition of tocilizumab to usual care was associated with a reduced death rate (9.5%) compared to those received only usual care (23.0%), with an adjusted hazard ratio (aHR) of 0.37 (95% confidence interval [CI], 0.15 to 0.91, P = 0.029). Combination therapy of tocilizumab and corticosteroids was associated with a significantly reduced fatality (aHR, 0.21; 95% CI, 0.08 to 0.56; P = 0.002) compared to those receiving corticosteroids alone. CONCLUSIONS: A significant benefit of reducing fatality in severe SFTS patients was observed by using tocilizumab. A combined therapy of tocilizumab plus corticosteroids was recommended for the therapy of severe SFTS.


Assuntos
Corticosteroides , Anticorpos Monoclonais Humanizados , Quimioterapia Combinada , Febre Grave com Síndrome de Trombocitopenia , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Febre Grave com Síndrome de Trombocitopenia/tratamento farmacológico , Febre Grave com Síndrome de Trombocitopenia/mortalidade , Corticosteroides/uso terapêutico , Corticosteroides/administração & dosagem , Idoso , Resultado do Tratamento , Hospitalização/estatística & dados numéricos , China , Adulto
15.
BMC Chem ; 18(1): 97, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715128

RESUMO

Modification of marketed drugs is an important way to develop drugs because its safety and clinical applicability. Oxygen-nitrogen heterocycles are a class of important active substances discovered in the process of new drug development. Dolutegravir, an HIV drug with a nitrogen-oxygen heterocycle structure, has the potential ability to inhibit cell survival. In order to find and explore novel anti-tumor drugs, new dolutegravir derivatives bearing different 1,2,3-triazole moieties were prepared via click reactions. In vitro biological experiments performed in several lung cancer cell lines suggested that these novel compounds displayed potent anti-tumor ability. Especially, the compound 9e with a substituent of 2-methyl-3-nitrophenyl and the compound 9p with a substituent of 3-trifluoromethylphenyl were effective against PC-9 cell line with IC50 values of 3.83 and 3.17 µM, respectively. Moreover, compounds 9e and 9p were effective against H460 and A549 cells. Further studies suggested that compounds 9e and 9p could induce cancer cell apoptosis in PC-9 and H460, inhibit cancer cell proliferation, change the cell cycle, and increase the level of reactive oxygen species (ROS) which further induce tumor cell apoptosis. In addition, compounds 9e and 9p increased LC3 protein expression which was the key regulator in autophagy signaling pathway in PC-9 cells. Compound 9e also showed low toxicity against normal cells, and could be regarded as an interesting lead compound for further structure optimization.

16.
Brain Behav ; 14(5): e3515, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38702895

RESUMO

INTRODUCTION: Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin (Mel) has been shown to have anti-inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD-induced cognitive impairment and its mechanisms are unknown. METHODS: In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61-88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription-polymerase chain reaction and western blotting. RESULTS: The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)-1creIL-6, and tumor necrosis factor-α and decreased the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels. CONCLUSIONS: These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction.


Assuntos
Hipocampo , Melatonina , Transtornos da Memória , Plasticidade Neuronal , Privação do Sono , Animais , Melatonina/farmacologia , Melatonina/administração & dosagem , Privação do Sono/complicações , Privação do Sono/tratamento farmacológico , Privação do Sono/fisiopatologia , Camundongos , Masculino , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Feminino , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Transtornos da Memória/fisiopatologia , Plasticidade Neuronal/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Gravidez , Privação Materna , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico
17.
J Biomed Res ; : 1-10, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38808546

RESUMO

Despite achieving a high cure rate with direct-acting antivirals (DAAs) in hepatitis C treatment, further research is needed to identify additional benefits of the DAA therapy. The current study evaluated liver fibrosis improvement in 848 hepatitis C patients treated with DAAs, who also achieved sustained virologic response (SVR). Using the fibrosis-4 (FIB-4) index, patients were categorized based on their baseline fibrosis level, and improvements in fibrosis were analyzed in both the short-term (9-26 weeks) and long-term (≥ 36 weeks) follow-up. The results showed a significant decrease in the FIB-4 index, indicating an improvement in liver fibrosis, in 63.00% of the patients during the short-term follow-up and 67.56% during the long-term follow-up. Short-term improvement was associated with factors including ribavirin (RBV) usage, blood cholinesterase levels, alanine transaminase levels, albumin levels, and the baseline FIB-4 index. Additionally, long-term improvement was associated with factors such as aspartate transaminase levels, total protein level, and the baseline FIB-4 index. The current study emphasizes the importance of continuous assessment and post-treatment monitoring of liver fibrosis, providing crucial insights for enhancing patient care in hepatitis C management.

18.
J Colloid Interface Sci ; 669: 275-282, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38718581

RESUMO

The triboelectric nanogenerator (TENG) of natural biomaterials is a new type of energy harvesting device and can be used as a self-powered sensor, which has received extensive research and attention. In this paper, based on the biocompatibility of chitosan and chondroitin sulfate, ZnO-modified chitosan/chondroitin sulfate/ZnO TENG was prepared for research on wearable devices and sustainable power supply devices. This study employs molecular dynamics to compute the interaction energy between chitosan and ZnO molecules. Theoretical calculations have unequivocally substantiated the occurrence of a binding interaction between these two molecular entities. The effect of ZnO on chitosan/chondroitin sulfate morphology was investigated by atomic force microscopy. The chitosan/chondroitin sulfate/ZnO TENG has high flexibility and electrical output performance. It can reach 105 V and 3.3 µA of open-circuit voltage and short-circuit current. Chitosan/chondroitin Sulfate/ZnO TENG successfully converts the mechanical energy of human motion into electrical energy. Strong electrical signals are exhibited when making fists and waving fingers and wrists. The TENG is a self-powered source and lights up 70 blue light-emitting diodes (LEDs). The chitosan/chondroitin sulfate/ZnO TENG has demonstrated its capabilities in energy harvesting and wearable self-powered sensors.

19.
J Ethnopharmacol ; 331: 118327, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750987

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Rohdea pachynema F.T.Wang & Tang (R. pachynema), is a traditional folk medicine used for the treatment of stomach pain, stomach ulcers, bruises, and skin infections in China. Some of the diseases may relate to microbial infections in traditional applications. However few reports on its antimicrobial properties and bioactive components. AIM OF THE STUDY: To identify its bioactive constituents against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo, and its mechanism. MATERIALS AND METHODS: The anti-MRSA ingredient 6α-O-[ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-quinovopyranosyl]-(25S)-5α-spirostan-3ß-ol (XQS) was obtained from R. pachynema by phytochemical isolation. Subsequently, XQS underwent screening using the broth microdilution method and growth inhibition curves to assess its antibacterial activity. The mechanism of XQS was evaluated by multigeneration induction, biofilm resistance assay, scanning electron microscopy, transmission electron microscopy, and metabolomics. Additionally, a mouse skin infection model was established in vivo. RESULTS: 26 compounds were identified from the R. pachynema, in which anti-MRSA spirostane saponin (XQS) was reported for the first time with a minimum inhibitory concentration (MIC) of 8 µg/mL. XQS might bind to peptidoglycan (PGN) of the cell wall, phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) of the cell membrane, then destroying the cell wall and the cell membrane, resulting in reduced membrane fluidity and membrane depolarization. Furthermore, XQS affected MRSA lipid metabolism, amino acid metabolism, and ABC transporters by metabolomics analysis, which targeted cell walls and membranes causing less susceptibility to drug resistance. Furthermore, XQS (8 mg/kg) recovered skin wounds in mice infected by MRSA effectively, superior to vancomycin (8 mg/kg). CONCLUSIONS: XQS showed anti-MRSA bioactivity in vitro and in vivo, and its mechanism association with cell walls and membranes was reported for the first, which supported the traditional uses of R. pachynema and explained its sensitivity to MRSA.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Saponinas , Animais , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/isolamento & purificação , Camundongos , Saponinas/farmacologia , Saponinas/isolamento & purificação , Espirostanos/farmacologia , Espirostanos/isolamento & purificação , Biofilmes/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Feminino , Peixes , Masculino
20.
Plant Commun ; 5(7): 100891, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38561965

RESUMO

Plants that grow in extreme environments represent unique sources of stress-resistance genes and mechanisms. Ammopiptanthus mongolicus (Leguminosae) is a xerophytic evergreen broadleaf shrub native to semi-arid and desert regions; however, its drought-tolerance mechanisms remain poorly understood. Here, we report the assembly of a reference-grade genome for A. mongolicus, describe its evolutionary history within the legume family, and examine its drought-tolerance mechanisms. The assembled genome is 843.07 Mb in length, with 98.7% of the sequences successfully anchored to the nine chromosomes of A. mongolicus. The genome is predicted to contain 47 611 protein-coding genes, and 70.71% of the genome is composed of repetitive sequences; these are dominated by transposable elements, particularly long-terminal-repeat retrotransposons. Evolutionary analyses revealed two whole-genome duplication (WGD) events at 130 and 58 million years ago (mya) that are shared by the genus Ammopiptanthus and other legumes, but no species-specific WGDs were found within this genus. Ancestral genome reconstruction revealed that the A. mongolicus genome has undergone fewer rearrangements than other genomes in the legume family, confirming its status as a "relict plant". Transcriptomic analyses demonstrated that genes involved in cuticular wax biosynthesis and transport are highly expressed, both under normal conditions and in response to polyethylene glycol-induced dehydration. Significant induction of genes related to ethylene biosynthesis and signaling was also observed in leaves under dehydration stress, suggesting that enhanced ethylene response and formation of thick waxy cuticles are two major mechanisms of drought tolerance in A. mongolicus. Ectopic expression of AmERF2, an ethylene response factor unique to A. mongolicus, can markedly increase the drought tolerance of transgenic Arabidopsis thaliana plants, demonstrating the potential for application of A. mongolicus genes in crop improvement.


Assuntos
Secas , Fabaceae , Genoma de Planta , Fabaceae/genética , Fabaceae/fisiologia , Estresse Fisiológico/genética , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Filogenia
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