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1.
Plant J ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38923617

RESUMO

Flavonols are widely synthesized throughout the plant kingdom, playing essential roles in plant physiology and providing unique health benefits for humans. Their glycosylation plays significant role in improving their stability and solubility, thus their accumulation and function. However, the genes encoding the enzymes catalyze this glycosylation remain largely unknown in apple. This study utilized a combination of methods to identify genes encoding such enzymes. Initially, candidate genes were selected based on their potential to encode UDP-dependent glycosyltransferases (UGTs) and their expression patterns in response to light induction. Subsequently, through testing the in vitro enzyme activity of the proteins produced in Escherichia coli cells, four candidates were confirmed to encode a flavonol 3-O-galactosyltransferase (UGT78T6), flavonol 3-O-glucosyltransferase (UGT78S1), flavonol 3-O-xylosyltransferase/arabinosyltransferase (UGT78T5), and flavonol 3-O-rhamnosyltransferase (UGT76AE22), respectively. Further validation of these genes' functions was conducted by modulating their expression levels in stably transformed apple plants. As anticipated, a positive correlation was observed between the expression levels of these genes and the content of specific flavonol glycosides corresponding to each gene. Moreover, overexpression of a flavonol synthase gene, MdFLS, resulted in increased flavonol glycoside content in apple roots and leaves. These findings provide valuable insights for breeding programs aimed at enriching apple flesh with flavonols and for identifying flavonol 3-O-glycosyltransferases of other plant species.

2.
J Exp Bot ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780282

RESUMO

Paclitaxel (PTX) is a high value plant natural product (PNP) derived from Taxus (yew) species. This plant secondary metabolite (PSM) and its derivatives constitute a cornerstone for the treatment of an increasing variety of cancers. New applications for PTX also continue to emerge, further promoting demand for this WHO designated essential medicine. Here we review recent advances in our understanding of PTX biosynthesis and its cognate regulation, which have been enabled by the development of transcriptomic approaches and the recent sequencing and annotation of three Taxus genomes. Collectively, this has resulted in the elucidation of two functional gene sets for PTX biosynthesis, unlocking new potential for the use of heterologous hosts to produce PTX. Knowledge of the PTX pathway also provides a valuable resource for understanding the regulation of this key PSM. Epigenetic regulation of PSM in plant cell culture (PCC) is a major concern for PTX production, given the loss of PSM production in long-term cell cultures. Recent developments aim to design tools for manipulating epigenetic regulation, potentially providing a means to reverse the silencing of PSM caused by DNA methylation. Exciting times clearly lie ahead for our understanding of this key PSM and improving its production potential.

3.
Langmuir ; 40(19): 10024-10034, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38698547

RESUMO

Responsive Pickering emulsions, with unique nanoparticle interfaces and sensitivity to external stimuli, significantly enhanced the stability and applicability of Pickering emulsions. Multifunctional composite material poly((2-(dimethylaminoethyl methacrylate)-b-(acrylate cyclodextrin))/Fe3O4 nanoparticles, namely P(DMAEMA-b-A-CD)/Fe3O4, with both multiresponsive characteristics and emulsifying capabilities had been designed to remove small oil droplets from water. Using the reversible addition-fragmentation chain transfer (RAFT) method, diblock polymers P(DMAEMA-b-A-CD) were grown in a controlled manner on the surface of Fe3O4. The Fe3O4 core showed responsiveness to a magnetic field, and the block copolymers prepared via the RAFT method demonstrated reactivity to both pH and CO2. The P(DMAEMA-b-A-CD)/Fe3O4 nanoparticles exhibited the capability to form Pickering/Oxford emulsions with exceptional stabilization properties. It could be observed that the introduction of CO2, acid, and a magnetic field led to the breakage of the emulsion, while the emulsion could be restabilized by removing the CO2 and the magnetic field or by adding alkali. Measurements of interfacial tension, ζ-potential, and contact angle demonstrated that the emulsification/breakdown mechanisms associated with pH and CO2/N2 were related to the surface wettability of the nanoparticles. In addition, the emulsifier had an excellent cycling capacity with at least 10 cycles by CO2/N2. Additionally, P(DMAEMA-b-A-CD)/Fe3O4 nanoparticles exhibited excellent stability in oil phases with large polarity differences and various real oil phases with different viscosities. Importantly, the P(DMAEMA-b-A-CD)/Fe3O4 nanoparticles could serve as functional materials for efficiently separating small oil droplets from water through the application of a magnetic field. Therefore, P(DMAEMA-b-A-CD)/Fe3O4 nanoparticles held promising potential as materials with economic and commercial value for oil-water separation applications.

4.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 66-72, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836680

RESUMO

This study aimed to investigate the mechanism of the effect of TREM2 on cognitive function in autistic mice. TREM2 overexpression and knockdown viruses were given to autism spectrum disorder (ASD) mice and BV2 microglia cell line. To assess cognitive performance, all groups of mice took part in the open field, new object recognition, Morris water maze, and three-box social experiments. Double immunofluorescence labeling demonstrated co-localization of LC3II and NeuN. Proteins from the PI3K/Akt/mTOR pathway were identified. In vivo, behavior studies revealed that TREM2 could successfully improve ASD mice's social interaction and cognitive performance. Besides, we discovered that TREM2 could increase autophagy in ASD mice. In vitro, overexpressing TREM2 reduced the expression of PI3K/AKT/mTOR pathway proteins, whereas knocking down TREM2 increased the expression of PI3K/AKT/mTOR pathway proteins. In conclusion, TREM2 could inhibit PI3K/Akt/mTOR signaling pathway, enhance autophagy, and improve the social communication ability and cognitive function of ASD mice.


Assuntos
Autofagia , Cognição , Glicoproteínas de Membrana , Microglia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Receptores Imunológicos , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Cognição/fisiologia , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Fosfatidilinositol 3-Quinases/metabolismo , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Serina-Treonina Quinases TOR/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos , Microglia/metabolismo , Masculino , Transtorno Autístico/metabolismo , Transtorno Autístico/genética , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/psicologia , Modelos Animais de Doenças , Comportamento Animal , Linhagem Celular , Camundongos Endogâmicos C57BL , Comportamento Social
5.
Med Sci Monit ; 30: e945269, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38808453

RESUMO

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Haijin Huang, Cuicui Hu, Lin Xu, Xiaoping Zhu, Lili Zhao, Jia Min. The Effects of Hesperidin on Neuronal Apoptosis and Cognitive Impairment in the Sevoflurane Anesthetized Rat are Mediated Through the PI3/Akt/PTEN and Nuclear Factor-kappaB (NF-kappaB) Signaling Pathways. Med Sci Monit, 2020; 26: e920522. DOI: 10.12659/MSM.920522.


Assuntos
Apoptose , Disfunção Cognitiva , Hesperidina , NF-kappa B , Neurônios , PTEN Fosfo-Hidrolase , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Sevoflurano , Transdução de Sinais , Animais , Sevoflurano/farmacologia , Apoptose/efeitos dos fármacos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Disfunção Cognitiva/metabolismo , Ratos , Hesperidina/farmacologia , Masculino , Fosfatidilinositol 3-Quinases/metabolismo
6.
BMC Health Serv Res ; 24(1): 94, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233772

RESUMO

BACKGROUND: While financial toxicity (FT) is prevalent in patients with cancer, young and middle-aged patients with stroke are also affected by FT, which can exacerbate their physical and psychological challenges. Understanding the patient's experience and response measures can further understand the impact of FT on patients with stroke, to help alleviate FT. However, little is known concerning the experience of patients with stroke with FT or their coping strategies. Therefore, this study aimed to describe the experiences of FT in young and middle-aged patients with stroke and their coping strategies. METHODS: A phenomenological method was utilized. Semi-structured interviews were conducted with 21 young and middle-aged stroke patients (aged 18-59) between October 2022 and March 2023. The participants were recruited from a tertiary hospital in Shanghai, China. The research team used NVivo 12.0 software. Giorgi's phenomenological analysis method was used to analyse the interview data. RESULTS: The interview results were divided into two categories in terms of patients' experiences of FT and their coping strategies. Nine subthemes were constructed. The experience category included four subthemes: (1) taking on multifaceted economic pressure, (2) dual choice of treatment, (3) decline in material living standards, and (4) suffering from negative emotions such as anxiety and depression. The coping strategy category included five subthemes: (1) reducing expenses, (2) improving living habits, (3) proactive participation in medical decision-making, (4) making a job position choice, and (5) seeking social support. CONCLUSIONS: FT in young and middle-aged patients with stroke, which affected their physical and mental health, led them to implement strategies for dealing with FT. The Chinese government needs to broaden the reach of health insurance coverage and advance the fairness of healthcare policies. Healthcare professionals must pay active attention to FT in such patients in terms of strengthening their health education and considering their needs and preferences. Patients need to improve their sense of self-efficacy, actively reintegrate into society, and adhere to rehabilitation and treatment. Individuals at a high risk of stroke are recommended to purchase health insurance. Multifaceted efforts are needed to reduce the impact of FT in young and middle-aged patients with stroke.


Assuntos
Capacidades de Enfrentamento , Acidente Vascular Cerebral , Pessoa de Meia-Idade , Humanos , Adaptação Psicológica , Estresse Financeiro , China , Acidente Vascular Cerebral/terapia , Pesquisa Qualitativa
7.
Artigo em Inglês | MEDLINE | ID: mdl-38401093

RESUMO

Objective: Analyzing the impact of nursing workforce development, training and standardization on hybrid operating theatres. Methods: Thirty nurses in the mixed operating room of the First Affiliated Hospital of Nanchang University from January 2021 to December 2021 were selected as the control group to receive routine nursing management and training methods and another thirty nurses were selected as the experimental group to receive nursing team construction, training and standardized management based on conventional methods. Nurses' theoretical and operational scores, nurses' satisfaction, surgeon satisfaction with nurses, and nursing service quality scores were compared between two groups at baseline and after intervention. Results: After the intervention, nurses in both groups had a significant improvement in theoretical and operational scores than those at baseline, and nurses in the experimental group had better scores than those in the control group, The difference was statistically significant (P = .002, P = .004). Nursing quality of surgical preparation, environmental management, surgical safety, and instrument management in the intervention group were significantly better than those at baseline and better than those in the control group. The difference was statistically significant (P = .001, P = .001, P = .001, P = .001). Satisfaction of nurses and doctors in the intervention group was significantly better than those at baseline and better than those in the control group. The difference was statistically significant (P = .002, P = .001). Conclusion: The effect of nursing team construction and training and standardized management of hybrid operating Room was ideal, which can improve nurses' theoretical knowledge and practical skills, and enhance the satisfaction of nurses and surgeons, providing patients with higher quality nursing services, which is worth adopting.

8.
Plant Dis ; 108(6): 1769-1775, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38240655

RESUMO

Watermelon silver mottle virus (WSMoV), a potentially invasive virus, is known to reduce the yield and degrade the quality of infected crops in Cucurbitaceae and Solanaceae families, resulting in significant economic losses in limited areas of several Asian countries. WSMoV, previously detected on various crops in southern China, has now become more prevalent on watermelon and sweet pepper in the northern cities of China for the first time. A sequencing-based phylogenetic analysis has confirmed that the viral strains infecting cucumber, watermelon, and sweet pepper plants in Shandong Province are most closely related to those isolated from Guangdong, Guangxi, and Taiwan, suggesting a farther and continuous spread of WSMoV throughout China. To develop a fast, accurate, and practical protocol for WSMoV detection, we designed a set of primers from the conserved sequence of the WSMoV nucleocapsid protein (N) gene for a one-step assay based on reverse transcription loop-mediated isothermal amplification (RT-LAMP). The RT-LAMP assay was performed successfully for 50 min at 61°C and exhibited a highly specific result without cross-reactions with other similar viruses and a sensitivity that is 100-fold higher than that of the traditional RT-PCR. The confirmation of 26 WSMoV suspect samples collected from various regions in Shandong through the RT-LAMP testing has demonstrated that the assay is suitable and practical for detection of WSMoV in both laboratory and field settings.


Assuntos
Citrullus , Técnicas de Amplificação de Ácido Nucleico , Filogenia , Doenças das Plantas , Doenças das Plantas/virologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Citrullus/virologia , China , Transcrição Reversa , Tospovirus/genética , Tospovirus/isolamento & purificação , Tospovirus/classificação , RNA Viral/genética , Capsicum/virologia , Técnicas de Diagnóstico Molecular
9.
BMC Med Educ ; 24(1): 32, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183036

RESUMO

BACKGROUND: Virtual simulation and face-to-face simulation are effective for clinical judgment training. Rare studies have tried to improve clinical judgment ability by applying virtual simulation and face-to-face simulation together. This study aimed to evaluate the effect of an integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program on enhancing nursing students' clinical judgment ability and understanding of nursing students' experiences of the combined simulation. METHODS: A sequential exploratory mixed-methods study was conducted in a nursing simulation center of a university in Central China. Third-year nursing students (n = 122) taking clinical training in ICUs were subsequentially assigned to the integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program arm (n = 61) or the face-to-face simulation-only arm (n = 61) according to the order in which they entered in ICU training. Clinical judgment ability was measured by the Lasater Clinical Judgment Rubric (LCJR). Focus group interviews were conducted to gather qualitative data. RESULTS: Students in both arms demonstrated significant improvement in clinical judgment ability scores after simulation, and students in the integrated arm reported more improvement than students in the face-to-face simulation-only arm. The qualitative quotes provided a context for the quantitative improvement measured by the LJCR in the integrated arm. Most of the quantitative findings were confirmed by qualitative findings, including the domains and items in the LJCR. The findings verified and favored the effect of the combination of non-immersive virtual simulation and high-fidelity face-to-face simulation integrated program on enhancing nursing students' clinical judgment ability. CONCLUSIONS: The integrated virtual simulation and face-to-face simulation program was feasible and enhanced nursing students' self-reported clinical judgment ability. This integrated non-immersive virtual simulation and high-fidelity face-to-face simulation program may benefit nursing students and newly graduated nurses in the ICU more than face-to-face simulation only.


Assuntos
Bacharelado em Enfermagem , Estudantes de Enfermagem , Humanos , Julgamento , China , Raciocínio Clínico
10.
Drug Dev Res ; 85(2): e22169, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38477422

RESUMO

Neutrophils are a crucial component of the innate immune system and play a pivotal role in various physiological processes. From a physical perspective, hitchhiking is considered a phenomenon of efficient transportation. The combination of neutrophils and hitchhikers has given rise to effective delivery systems both in vivo and in vitro, thus neutrophils hitchhiking become a novel approach to disease treatment. This article provides an overview of the innovative and feasible application of neutrophils as drug carriers. It explores the mechanisms underlying neutrophil function, elucidates the mechanism of drug delivery mediated by neutrophil-hitchhiking, and discusses the potential applications of this strategy in the treatment of cancer, immune diseases, inflammatory diseases, and other medical conditions.


Assuntos
Nanopartículas , Neoplasias , Humanos , Neutrófilos , Sistemas de Liberação de Medicamentos , Portadores de Fármacos , Nanopartículas/uso terapêutico
11.
J Environ Manage ; 365: 121568, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38936024

RESUMO

Adding fruit tree branches to the compost pile in appropriate proportions is one of the methods used to address the challenge of tobacco waste recycling. However, the effects of different proportions of fruit tree branches on nicotine concentration and microbial diversity during tobacco waste composting have not been reported. In this study, a composting system with tobacco waste, cow dung, and fruit tree branches was established in a laboratory fermenter to assess the impact of adding 10%, 20%, and 30% fruit tree branches on quantity changes. In addition, the relationships between nicotine degradation, compost properties, enzyme activities, and microbial diversities were determined using biochemical assay methods and high-throughput sequencing. The results showed that adding appropriate proportions of fruit branch segments affected changes in physical and chemical properties during composting and promoted tobacco waste compost maturity. Aerobic composting effectively degraded nicotine in tobacco waste. Increased proportions of fruit branch segments led to elevations in nicotine degradation rates and enzyme activities related to lignocellulose degradation. The addition of fruit branches influenced the relative abundance and species of dominant bacteria and fungi at the phylum and genus levels. However, it did not significantly affect the relative abundance of the main bacterial genera involved in nicotine degradation. Nevertheless, it reduced the sensitivity of enzyme activity to nicotine content within heaps, increasing reliance on total nitrogen changes. The results of this study provide a theoretical basis for the utilization of tobacco waste in composting systems and indicate that fruit tree branches can enhance nicotine degradation efficiency during tobacco waste composting.

12.
J Environ Manage ; 359: 120962, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38677229

RESUMO

Low-water-level regulation has been effectively implemented in the restoration of urban river sediments in Guangzhou City, China. Further investigation is needed to understand the microbial mechanisms involved in pollutant degradation in low-water-level environments. This study examined sediment samples from nine rivers, including low-water-level rivers (LW), tidal waterways (TW), and enclosed rivers (ER). Metagenomic high-throughput sequencing and the Diting pipeline were utilized to investigate the microbial mechanisms involved in sediment C/N/S geochemical cycling during low-water-level regulation. The results reveal that the degree of pollution in LW sediment is lower compared to TW and ER sediment. LW sediment exhibits a higher capacity for pollutant degradation and elimination of black, odorous substances due to its stronger microbial methane oxidation, nitrification, denitrification, anammox, and oxidation of sulfide, sulfite, and thiosulfate. Conversely, TW and ER sediment showcase greater microbial methanogenesis, anaerobic fermentation, and sulfide generation abilities, leading to the persistence of black, odorous substances. Factors such as grit and silt content, nitrate, and ammonia concentrations impacted microbial metabolic pathways. Low-water-level regulation improved the micro-environment for functional microbes, facilitating pollutant removal and preventing black odorous substance accumulation. These findings provide insights into the microbial mechanisms underlying low-water-level regulation technology for sediment restoration in urban rivers.


Assuntos
Sedimentos Geológicos , Rios , Sedimentos Geológicos/microbiologia , Nitrogênio/análise , Carbono , China
13.
Clin Immunol ; 256: 109780, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37741520

RESUMO

NKG2D provides a costimulatory signal for activation of CD4+ T cells. We explored its role in interactions of CD4+ T cells and dendritic cells (DCs) in juvenile idiopathic arthritis (JIA) patients by using NKG2D genetically modified CD4+ T cells. We found active JIA patients had significantly higher content of CD4 + NKG2D+ T cells than healthy controls. Expression of NKG2D on CD4+ T cells, and MICA and MICB on DCs were significantly greater in articular JIA than systemic JIA. NKG2D induced IL- 12 and suppressed IL-10 and TGF-ß from CD4+ T cells, increased IFN-γ + CD4+ T and IL-17+ CD4+ T cells, RORc and T-bet, but reduced CD25+ Foxp3+ CD4+ T cells, IL-4+ CD4+ T cells, Foxp3, and GATA3 in JIA patients. NKG2D decreased IL-10 and increased CD83, MICA, and MICB of DCs in JIA and controls. So NKG2D regulates differentiation of CD4+ T cells directly and the maturation of DCs indirectly.


Assuntos
Artrite Juvenil , Humanos , Diferenciação Celular , Células Dendríticas/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Interleucina-10/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Linfócitos T Reguladores/metabolismo
14.
Respir Res ; 24(1): 272, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37932762

RESUMO

BACKGROUND: SARS-CoV-2, the agent responsible for the COVID-19 pandemic, enters cells through viral spike glycoprotein binding to the cellular receptor, angiotensin-converting enzyme 2 (ACE2). Given the lack of effective antivirals targeting SARS-CoV-2, we previously utilized systematic evolution of ligands by exponential enrichment (SELEX) and selected fluoro-arabino nucleic acid (FANA) aptamer R8-9 that was able to block the interaction between the viral receptor-binding domain and ACE2. METHODS: Here, we further assessed FANA-R8-9 as an entry inhibitor in contexts that recapitulate infection in vivo. RESULTS: We demonstrate that FANA-R8-9 inhibits spike-bearing pseudovirus particle uptake in cell lines. Then, using an in-vitro model of human airway epithelium (HAE) and SARS-CoV-2 virus, we show that FANA-R8-9 significantly reduces viral infection when added either at the time of inoculation, or several hours later. These results were specific to the R8-9 sequence, not the xeno-nucleic acid utilized to make the aptamer. Importantly, we also show that FANA-R8-9 is stable in HAE culture secretions and has no overt cytotoxic effects. CONCLUSIONS: Together, these results suggest that FANA-R8-9 effectively prevents infection by specific SARS-CoV-2 variants and indicate that aptamer technology could be utilized to target other clinically-relevant viruses in the respiratory mucosa.


Assuntos
COVID-19 , Ácidos Nucleicos , Humanos , COVID-19/metabolismo , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/metabolismo , Ácidos Nucleicos/metabolismo , Pandemias/prevenção & controle , Ligação Proteica , Mucosa Respiratória/metabolismo , Epitélio/metabolismo
15.
Mol Cell Biochem ; 478(4): 927-937, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36114991

RESUMO

Activated cardiac fibroblasts are involved in both reparative wound healing and maladaptive cardiac fibrosis after myocardial infarction (MI). Recent evidence suggests that PU.1 inhibition can enable reprogramming of profibrotic fibroblasts to quiescent fibroblasts, leading to attenuation of pathologic fibrosis in several fibrosis models. The role of PU.1 in acute MI has not been tested. We designed a randomized, blinded study to evaluate whether DB1976, a PU.1 inhibitor, attenuates cardiac function deterioration and fibrosis in a murine model of MI. A total of 44 Ai9 periostin-Cre transgenic mice were subjected to 60 min of coronary occlusion followed by reperfusion. At 7 days after MI, 37 mice were randomly assigned to control (vehicle) or DB1976 treatment and followed for 2 weeks. Left ventricular ejection fraction (EF), assessed by echocardiography, did not differ between the two groups before or after treatment (final EF, 33.3 ± 1.0% in control group and 31.2 ± 1.3% in DB1976 group). Subgroup analysis of female and male mice showed the same results. There were no differences in cardiac scar (trichrome stain) and fibrosis (interstitial/perivascular collagen; picrosirius stain) between groups. Results from the per-protocol dataset (including mice with pre-treatment EF < 35% only) were consistent with the full dataset. In conclusion, this randomized, blinded study demonstrates that DB1976, a PU.1 inhibitor, does not attenuate cardiac functional deterioration or cardiac fibrosis in a mouse model of MI caused by coronary occlusion/reperfusion.


Assuntos
Oclusão Coronária , Infarto do Miocárdio , Camundongos , Masculino , Feminino , Animais , Volume Sistólico , Oclusão Coronária/patologia , Modelos Animais de Doenças , Função Ventricular Esquerda , Infarto do Miocárdio/patologia , Camundongos Transgênicos , Fibrose , Miocárdio/patologia , Camundongos Endogâmicos C57BL , Remodelação Ventricular
16.
Clin Transplant ; 37(11): e15121, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37676427

RESUMO

OBJECTIVE AND BACKGROUND: BK virus-associated hemorrhagic cystitis (BKV-HC) is an intractable complication leading to higher mortality and prolonged hospitalization among allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients. Therefore, identifying the potential risk factors of BKV-HC after allo-HCT is crucial to improve prognosis and for early prevention. However, the risk factors for BKV-HC remain debatable. Therefore, we conducted a systematic review and meta-analysis to identify the risk factors for BKV-HC, for early prevention of the occurrence of BKV-HC and to improve the quality of life and prognosis of allo-HCT recipients. METHODS: We searched relevant studies from PubMed, EMBASE, and the Cochrane Library up to February 2023. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of all risk factors were calculated to evaluate their effects on the occurrence of BKV-HC. RESULTS: Overall, 11 studies involving 2556 allo-HCT recipients were included in this meta-analysis. All included studies were retrospective and published between 2013 and 2022. We found that male sex (OR = 1.32; 95% CI, 1.07-1.62; p = .009, I2  = 34%), haploidentical donor (OR = 1.84; 95% CI, 1.18-2.87; p = .007, I2  = 23%), myeloablative conditioning (OR = 1.76; 95% CI, 1.36-2.28; p < .0001, I2  = 45%), acute graft versus host disease (aGVHD) (OR = 2.73; 95% CI, 2.02-3.69; p < .0001, I2  = 46%), chronic graft versus host disease (cGVHD) (OR = 1.71; 95% CI, 1.12-2.60; p = .01, I2  = 0%), and cytomegalovirus (CMV) reactivation (OR = 3.13; 95% CI, 1.12-8.78; p = .03, I2  = 79%) were significantly associated with BKV-HC in the univariable analysis. CONCLUSIONS: Our meta-analysis indicated that male sex, haploidentical donor, myeloablative conditioning, aGVHD, cGVHD, and CMV reactivation were potential risk factors for BKV-HC.


Assuntos
Vírus BK , Cistite , Infecções por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Masculino , Estudos Retrospectivos , Qualidade de Vida , Cistite/etiologia , Cistite/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Fatores de Risco , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/epidemiologia , Infecções por Citomegalovirus/etiologia , Infecções por Polyomavirus/epidemiologia , Infecções Tumorais por Vírus/epidemiologia
17.
J Immunol ; 207(5): 1310-1321, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34380652

RESUMO

The respiratory tract is constantly exposed to various airborne pathogens. Most vaccines against respiratory infections are designed for the parenteral routes of administration; consequently, they provide relatively minimal protection in the respiratory tract. A vaccination strategy that aims to induce the protective mucosal immune responses in the airway is urgently needed. The FcRn mediates IgG Ab transport across the epithelial cells lining the respiratory tract. By mimicking this natural IgG transfer, we tested whether FcRn delivers vaccine Ags to induce a protective immunity to respiratory infections. In this study, we designed a monomeric IgG Fc fused to influenza virus hemagglutinin (HA) Ag with a trimerization domain. The soluble trimeric HA-Fc were characterized by their binding with conformation-dependent HA Abs or FcRn. In wild-type, but not FcRn knockout, mice, intranasal immunization with HA-Fc plus CpG adjuvant conferred significant protection against lethal intranasal challenge with influenza A/PR/8/34 virus. Further, mice immunized with a mutant HA-Fc lacking FcRn binding sites or HA alone succumbed to lethal infection. Protection was attributed to high levels of neutralizing Abs, robust and long-lasting B and T cell responses, the presence of lung-resident memory T cells and bone marrow plasma cells, and a remarkable reduction of virus-induced lung inflammation. Our results demonstrate for the first time, to our knowledge, that FcRn can effectively deliver a trimeric viral vaccine Ag in the respiratory tract and elicit potent protection against respiratory infection. This study further supports a view that FcRn-mediated mucosal immunization is a platform for vaccine delivery against common respiratory pathogens.


Assuntos
Antígenos de Histocompatibilidade Classe I/metabolismo , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Infecções por Orthomyxoviridae/imunologia , Orthomyxoviridae/fisiologia , Receptores Fc/metabolismo , Mucosa Respiratória/metabolismo , Administração Intranasal , Animais , Anticorpos Antivirais/metabolismo , Modelos Animais de Doenças , Resistência à Doença , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Imunoglobulina G/metabolismo , Vacinas contra Influenza/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Fc/genética , Mucosa Respiratória/imunologia , Vacinação
18.
Curr Microbiol ; 80(9): 281, 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37439829

RESUMO

Lysobacter capsici X2-3, a plant growth-promoting rhizobacteria (PGPR), was isolated from wheat rhizosphere and has inhibitory effects against a wide range of pathogens. One important characteristic of L. capsici is its ability to produce diverse antibiotics and lytic enzymes. The GntR family of transcription factors is a common transcription factor superfamily in bacteria that has fundamental roles in bacterial metabolism regulation. However, the GntR family transcription factor in Lysobacter has not been identified. In this study, to obtain an understanding of the GntR/HutC gene function in L. capsici X2-3, a random Tn5-insertion mutant library of X2-3 was constructed to select genes showing pleiotropic effects on phenotype. We identified a Tn5 mutant with an insertion in LC4356 that showed reduced biofilm levels, and sequence analysis indicated that the inserted gene encodes a GntR/HutC family transcription regulator. Furthermore, the LC4356 mutant showed reduced extracellular polysaccharide (EPS) production, diminished twitching motility and decreased survival under UV radiation and high-temperature. The RT‒qPCR results indicated that the pentose phosphate pathway-related genes G6PDH, 6PGL and PGDH were upregulated in the LC4356 mutant. Thus, since L. capsici is an efficient biocontrol agent for crop protection, our findings provide fundamental insights into GntR/HutC and will be worthwhile to improve PGPR biocontrol efficacy.


Assuntos
Lysobacter , Lysobacter/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Bactérias/metabolismo , Biofilmes , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
19.
J Cardiothorac Vasc Anesth ; 37(10): 1996-2005, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37422336

RESUMO

OBJECTIVES: To investigate the effects of remimazolam on postoperative cognitive function, intraoperative hemodynamics, and oxygenation in older patients undergoing lobectomy. DESIGN: A prospective, double-blind, randomized, controlled study. SETTING: A university hospital. PARTICIPANTS: Eighty-four older patients with lung cancer who underwent lobectomy, aged ≥65 years. INTERVENTIONS: Patients were divided randomly into the remimazolam (group R) and propofol (group P) groups. Group R underwent remimazolam anesthesia induction and maintenance, whereas group P underwent propofol anesthesia induction and maintenance. Cognitive function was assessed with neuropsychological tests 1 day before surgery and 7 days after surgery. The Clock Drawing Test, Verbal Fluency Test (VFT), Digit Symbol Switching Test (DSST), and Auditory Verbal Learning Test-Huashan (AVLT-H) assessed visuospatial ability, language function, attention, and memory, respectively. The systolic blood pressure (SBP), heart rate, mean arterial pressure (MAP), and cardiac index were recorded 5 minutes before induction of anesthesia (T0), 2 minutes after sedation (T1), 5 minutes after intubation with two-lung ventilation (T2), 30 minutes after one-lung ventilation (OLV) (T3), 60 minutes after OLV (T4), and at the end of surgery (T5), and the incidences of hypotension and bradycardia were recorded. The PaO2, oxygenation index (OI), and intrapulmonary shunt (Qs/Qt) were assessed at T0, T2, T3, T4, and T5. The levels of S-100ß and interleukin 6 were measured by enzyme-linked immunosorbent assay at T0, T5, 24 hours after surgery (T6), and on day 7 after surgery (T7). MEASUREMENTS AND MAIN RESULTS: The VFT, DSST, immediate recall AVLT-H, and short-delayed recall AVLT-H scores were significantly higher in group R than in group P on day 7 after surgery (p < 0.05). The SBP and MAP at T2 to T5 were significantly higher in group R than in group P, the incidence of hypotension was significantly lower in group R (9.5%) than in group P (35.7%) (p = 0.004), and remimazolam significantly reduced the dose of phenylephrine used (p < 0.05). The PaO2 and OI at T4 were significantly higher in group R than in group P, and Qs/Qt was significantly lower in group R than in group P. The levels of S-100ß at T5 were significantly lower in group R than in group P (p < 0.05). CONCLUSION: The results showed that remimazolam (versus propofol) may lessen the degree of short-term postoperative cognitive dysfunction measured by standard neuropsychological tests, better optimize intraoperative hemodynamics, and lead to improved oxygenation during OLV.


Assuntos
Ventilação Monopulmonar , Propofol , Humanos , Idoso , Propofol/efeitos adversos , Ventilação Monopulmonar/métodos , Estudos Prospectivos , Subunidade beta da Proteína Ligante de Cálcio S100 , Pulmão/cirurgia , Hemodinâmica/fisiologia , Anestesia Geral/métodos , Cognição
20.
Aging Clin Exp Res ; 35(9): 1891-1899, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37365389

RESUMO

PURPOSE: The purpose of this study was to predict the probability of postoperative pulmonary infection in elderly patients with hip fractures by developing and validating a precise model. METHODS: The clinical data of 1008 elderly hip fracture patients undergoing surgical treatment in Shanghai Tenth Peoples' Hospital were retrospectively selected. A univariate analysis and multivariate regression were used to analyze the independent risk factors for postoperative pulmonary infection in elderly patients with hip fractures. A risk prediction model was established, and a nomogram was drawn. The area under the ROC curve and Hosmer‒Lemeshow test were used to evaluate the predictive effect of the model. RESULTS: The multivariate regression analysis indicated that age > 73, time from fracture to surgery (d) > 4 days, smoking, ASA ≥ III level, COPD, hypoproteinemia, red cell distribution width > 14.8%, mechanical ventilation time > 180 min, and stay in the ICU were independent risk factors for postoperative pulmonary infection in elderly patients. The AUCs of the model were 0.891 and 0.881, 0.843, respectively, in the two verification groups. For the Hosmer‒Lemeshow test, the P values were 0.726 in the modeling group and 0.497 and 0.231 in the verification group (P > 0.05). CONCLUSION: Overall, this study uncovered different independent risk factors for postoperative pulmonary infection in patients with hip fractures. The nomogram can effectively predict the occurrence of postoperative pulmonary infection.


Assuntos
Fraturas do Quadril , Pneumonia , Humanos , Idoso , Nomogramas , Estudos Retrospectivos , China , Fraturas do Quadril/cirurgia , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
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