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1.
Front Aging Neurosci ; 14: 996646, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185484

RESUMO

Pyroptosis is a form of cell death mediated by inflammasomes and gasdermins, and the relevance of pyroptosis to neurodegenerative diseases is currently receiving increasing attention. Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease that is closely associated with neuroinflammation. Its main pathological features include ß-amyloid (Aß) deposition, Tau protein hyperphosphorylation and neuronal loss. Aß, tau-induced microglia pyroptosis and polarization leading to neuroinflammation play an important role in the pathogenesis of AD. Studying the pathogenesis and treatment of AD based on cellular pyroptosis has become a new direction in AD research. In this paper, we review the research progress of pyroptosis and will focus on the pathogenic roles of pyroptosis in AD and the role of targeted inhibition of inflammasome-dependent pyroptosis in AD treatment. These results deepen our understanding of the pathogenesis of AD and provide ideas for the development of new drugs based on the regulation of pyroptosis in AD patients.

2.
Oxid Med Cell Longev ; 2022: 9010354, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36193058

RESUMO

Background: Bronchopulmonary dysplasia (BPD) is one of the most serious complications in premature infants. Myeloid-derived suppressor cells (MDSCs) have been indicated to promote immune tolerance and induce anti-inflammatory responses during the neonatal stage. However, the role of MDSCs in BPD has not been completely expounded. Methods: 130 cases of newborns were collected from six tertiary hospitals in Guangzhou from August 2019 to June 2022. They were divided into BPD group, non-BPD preterm infants group, and term infants group according to gestational age and presence of BPD. The peripheral blood was collected and used to analyze the proportion, phenotypic, and function of MDSCs at 3 to 7 days and 8 to 14 days after birth, respectively. Results: We indicated that the number of both MDSCs in premature infants is reduced, and the number of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in peripheral blood of BPD infants was significantly lower than that of non-BPD infants under 34 weeks of gestational age (P < 0.05). Furthermore, PMN-MDSCs from peripheral blood of patients presented inhibitory effect on proliferation of CD4+T and CD8+T cells in each group. However, PMN-MDSCs from BPD group had obviously weaker inhibitory effect on proliferation of CD4+T and CD8+T cells than that from non-BPD preterm infants group. In addition, we demonstrated that the expression of NADPH oxidase (Nox2) and reactive oxygen species (ROS) in PMN-MDSCs of BPD children was significantly lower than that in non-BPD preterm infants, suggesting that ROS pathway was affected in BPD in premature infants. Conclusion: This study preliminarily revealed the role of PMN-MDSCs in the pathogenesis of BPD in premature infants. The specific immune regulation mechanism of PMN-MDSCs in BPD will provide new ideas and strategies for clinical prevention and treatment of BPD in premature infants.


Assuntos
Displasia Broncopulmonar , Doenças do Prematuro , Células Supressoras Mieloides , Anti-Inflamatórios/metabolismo , Displasia Broncopulmonar/metabolismo , Criança , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/patologia , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/patologia , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo
3.
J Environ Public Health ; 2022: 2654437, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36193395

RESUMO

In recent years, college students' psychological problems have occurred frequently, and the early warning of college students' psychological crisis has received social attention. Artificial intelligence and big data, as emerging technologies that have attracted much attention in recent years, have broad application and development space in improving the development of intelligent and refined education in colleges and universities. Applying artificial intelligence and big data to the practice of college students' mental health education plays a very positive role in accurately finding and scientifically solving college students' mental health problems. This paper combs the current application and research of artificial intelligence and big data in college students' mental health education and then clarifies the problems existing in the practical application. Finally, on the basis of in-depth analysis of the characteristics of college students' psychological crisis, the paper designs college students' psychological crisis early warning data collection system from six aspects, including the educational administration system and the access control system. And from the aspects of establishing a multilevel linkage feedback early warning system, building a team of big data technical personnel and mental health education personnel, it puts forward countermeasures for college students' psychological crisis, so as to provide theoretical and methodological support for college mental health management.


Assuntos
Inteligência Artificial , Big Data , Emergências , Humanos , Estudantes/psicologia , Universidades
4.
Virus Res ; 322: 198945, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36181974

RESUMO

Vibrio alginolyticus is a common foodborne pathogen existing both in contaminated seafood and the environment and can cause serious mortality in aquaculture facilities. Bacteriophages can be used as an alternative bio-control agent to eliminate and reduce pathogens. In this study, a novel lytic phage, designated vB_ValP_VA-RY-3 (referred to as S1R3Y), was isolated from sewage collected in Dalian, China. The linear double-stranded DNA genome of phage S1R3Y is 40.271 kb, which has a mol% G + C content of 43.98, containing 51 ORFs with a T7-like genomic organization. It shared the closest relationship with phage vB_CsaP_Ss1, but the homology coverage is just 6%. S1R3Y lacks tRNA and no known virulence or lysogenic genes were found. S1R3Y had a burst size of 147 PFU/cell and is stable under different temperatures (4-56 °C) and pH (5.0-7.0). A comparison of its genomic features and phylogenetic analysis revealed that phage S1R3Y is a novel member of the order Caudovirales, family Podoviridae. Our results suggest that phage S1R3Y may represent a potential therapeutic agent against Vibrio alginolyticus.

5.
Acta Cir Bras ; 37(6): e370605, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36074398

RESUMO

PURPOSE: Traumatic brain injury (TBI) is a major cause of death and disability. Cerebrolysin (CBL) has been reported to be anti-inflammatory by reducing reactive oxygen species (ROS) production. However, the neuroprotection of CBL in TBI and the potential mechanism are unclear. We aimed to investigate the neuroprotection and mechanisms of CBL in TBI. METHODS: The TBI model was established in strict accordance with the Feeney weight-drop model of focal injury. The neurological score, brain water content, neuroinflammatory cytokine levels, and neuronal damage were evaluated. The involvement of the early brain injury modulatory pathway was also investigated. RESULTS: Following TBI, the results showed that CBL administration increased neurological scores and decreased brain edema by alleviating blood­brain barrier (BBB) permeability, upregulating tight junction protein (ZO­1) levels, and decreasing the levels of the inflammatory cytokines tumor necrosis factor­α (TNF­α), interleukin­1ß (IL­1ß), IL­6, and NF­κB. The TUNEL assay showed that CBL decreased hippocampal neuronal apoptosis after TBI and decreased the protein expression levels of caspase­3 and Bax, increasing the levels of Bcl­2. The levels of Toll­like receptor 2 (TLR2) and TLR4 were significantly decreased after CBL treatment. In TBI patients, CBL can also decrease TNF­α, IL­1ß, IL­6, and NF­κB levels. This result indicates that CBL­mediated inhibition of neuroinflammation and apoptosis ameliorated neuronal death after TBI. The neuroprotective capacity of CBL is partly dependent on the TLR signaling pathway. CONCLUSIONS: Taken together, the results of this study indicate that CBL can improve neurological outcomes and reduce neuronal death against neuroinflammation and apoptosis via the TLR signaling pathway in mice.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Fármacos Neuroprotetores , Aminoácidos , Animais , Apoptose , Encéfalo/metabolismo , Lesões Encefálicas/metabolismo , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Doenças Neuroinflamatórias , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
6.
Mikrochim Acta ; 189(10): 381, 2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098809

RESUMO

Different morphology of N-doped carbon materials, including three-dimensional interconnected N-doped hierarchically porous carbon networks (3D-NC), two-dimensional ultrathin porous carbon nanosheets (2D-NC), and bulk N-doped carbon with micron size (bulk-NC), was easily prepared by using NaCl crystal templates-assisted strategy. Compared with bare glassy carbon, bulk-NC, and 2D-NC, the as-synthesized 3D-NC exhibits excellent electrochemical activity toward the oxidation and sensing of three kinds of common environmental pollutants dihydroxybenzene isomers (hydroquinone (HQ), catechol (CC), and resorcinol (RS)). The impressive electrochemical activity of 3D-NC can be interpreted by its large specific surface area, continuous network-like morphology, superior electro-catalytic ability, and strong accumulation efficiency. Differential pulse voltammetry (DPV) test showed the 3D-NC-modified electrode exhibited three well-separated oxidation peaks at 0.05 V, 0.14 V, and 0.45 V vs. saturated calomel electrode (SCE) for HQ, CC, and RS, and their detection limits were evaluated to be as low as 0.0044, 0.012, and 0.016 mg L-1, respectively. Finally, a novel electrochemical analytical platform is successfully fabricated for the simultaneous monitoring of hydroquinone, catechol, and resorcinol with high sensitivity. When used for real wastewater samples analysis, recovery ratio ranging from 94 to 108% with lower than 5% of relative standard deviation (RSD) values was achieved. This work proves a facile strategy to prepare morphology-controlled N-doped carbon-based material and demonstrates its high application potential for environmental monitoring and electrochemical analysis.


Assuntos
Carbono , Hidroquinonas , Carbono/química , Catecóis/química , Hidroquinonas/química , Porosidade , Resorcinóis/análise
7.
Front Oncol ; 12: 915481, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046054

RESUMO

Endoscopic ultrasonography (EUS) is the most common method for diagnosing gastrointestinal subepithelial lesions (SELs); however, it usually requires histopathological confirmation using invasive methods. Artificial intelligence (AI) algorithms have made significant progress in medical imaging diagnosis. The purpose of our research was to explore the application of AI in the diagnosis of SELs using EUS and to evaluate the diagnostic performance of AI-assisted EUS. Three databases, PubMed, EMBASE, and the Cochrane Library, were comprehensively searched for relevant literature. RevMan 5.4.1 and Stata 17.0, were used to calculate and analyze the combined sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver-operating characteristic curve (SROC). Eight studies were selected from 380 potentially relevant studies for the meta-analysis of AI-aided EUS diagnosis of SELs. The combined sensitivity, specificity, and DOR of AI-aided EUS were 0.92 (95% CI, 0.85-0.96), 0.80 (95% CI, 0.70-0.87), and 46.27 (95% CI, 19.36-110.59), respectively). The area under the curve (AUC) was 0.92 (95% CI, 0.90-0.94). The AI model in differentiating GIST from leiomyoma had a pooled AUC of 0.95, sensitivity of 0.93, specificity of 0.88, PLR of 8.04, and NLR of 0.08. The combined sensitivity, specificity, and AUC of the AI-aided EUS diagnosis in the convolutional neural network (CNN) model were 0.93, 0.81, and 0.94, respectively. AI-aided EUS diagnosis using conventional brightness mode (B-mode) EUS images had a combined sensitivity of 0.92, specificity of 0.79, and AUC of 0.92. AI-aided EUS diagnosis based on patients had a combined sensitivity, specificity, and AUC of 0.95, 0.83, and 0.96, respectively. Additionally, AI-aided EUS was superior to EUS by experts in terms of sensitivity (0.93 vs. 0.71), specificity (0.81 vs. 0.69), and AUC (0.94 vs. 0.75). In conclusion, AI-assisted EUS is a promising and reliable method for distinguishing SELs, with excellent diagnostic performance. More multicenter cohort and prospective studies are expected to be conducted to further develop AI-assisted real-time diagnostic systems and validate the superiority of AI systems. Systematic Review Registration: PROSPERO (https://www.crd.york.ac.uk/PROSPERO/), identifier CRD42022303990.

8.
Molecules ; 27(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36080446

RESUMO

Since the outbreak of the COVID-19 pandemic, traditional Chinese medicine has played an important role in the treatment process. Furthermore, the discovery of artemisinin in Artemisia annua has reduced the incidence of malaria all over the world. Therefore, it is becoming urgent and important to establish a novel method of conducting systematic research on Chinese herbal medicine, improving the medicinal utilization value of traditional Chinese medicine and bringing great benefits to human health all over the world. Fructus Malvae, a kind of Chinese herbal medicine which has been recorded in the "Chinese Pharmacopoeia" (2020 edition), refers to the dry, ripe fruits of Malva verticillata L. Recently, some studies have shown that Fructus Malvae exhibits some special pharmacological activities; for example, it has diuretic, anti-diabetes, antioxidant and anti-tumor properties, and it alleviates hair loss. Furthermore, according to the reports, the active ingredients separated and identified from Fructus Malvae contain some very novel compounds such as nortangeretin-8-O-ß-d-glucuronopyranoside and 1-O-(6-deoxy-6-sulfo)-glucopyranosyl-2-O-linolenoyl-3-O-palmitoyl glyceride, which could be screened as important candidate compounds for diabetes- or tumor-treatment drugs, respectively. Therefore, in this research, we take Fructus Malvae as an example and systematically summarize the chemical constituents and pharmacological activity research progress of it. This review will be helpful in promoting the development and application of Fructus Malvae and will also provide an example for other investigations of traditional Chinese medicine.


Assuntos
COVID-19 , Medicamentos de Ervas Chinesas , COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Frutas , Humanos , Medicina Tradicional Chinesa , Pandemias
9.
BMC Gastroenterol ; 22(1): 409, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064316

RESUMO

BACKGROUND: T1 colorectal cancers have a low lymph node metastasis rate and good prognosis. Thus, endoscopic resection is an attractive choice. This study aimed to describe the value of poorly differentiated cluster grade in identifying endoscopically curable T1 colorectal cancers. METHODS: We included 183 T1 colorectal cancer patients who underwent curative resection. Univariate and multivariate logistic regressions were used to identify lymph node metastasis predictors. The Akaike information criterion was used to determine whether poorly differentiated cluster grade was the best predictor. Backward regression was used to screen the variables. Survival analyses were conducted to determine the prognostic predictive power of poorly differentiated cluster grade. Correlations among predictors and concordance between our pathologists were also investigated. RESULTS: Poorly differentiated cluster grade was an independent predictor for lymph node metastasis (adjusted odds ratio [OR]G 3 = 0.001; 95% confidence interval [95% CI]G 3 = < 0.001, 0.139) in T1 colorectal cancer patients; moreover, it had the best predictive value (AIC = 61.626) among all indicators. It was also screened for inclusion in the predictive model. Accordingly, a high poorly differentiated cluster grade independently indicated shorter overall survival (hazard ratio [HR]G 2 = 4.315; 95% CIG 2 = 1.506, 12.568; HRG 3 = 5.049; 95% CIG 3 = 1.326, 19.222) and disease-free survival (HRG 3 = 6.621; 95% CIG 3 = 1.472, 29.786). CONCLUSIONS: Poorly differentiated cluster grade is a vital reference to manage T1 colorectal cancer. It could serve as an indicator to screen endoscopically curable T1 colorectal cancers.


Assuntos
Neoplasias Colorretais , Neoplasias Colorretais/patologia , Humanos , Metástase Linfática , Prognóstico , Estudos Retrospectivos , Fatores de Risco
10.
Nat Immunol ; 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36138184

RESUMO

Naive T cells undergo radical changes during the transition from dormant to hyperactive states upon activation, which necessitates de novo protein production via transcription and translation. However, the mechanism whereby T cells globally promote translation remains largely unknown. Here, we show that on exit from quiescence, T cells upregulate transfer RNA (tRNA) m1A58 'writer' proteins TRMT61A and TRMT6, which confer m1A58 RNA modification on a specific subset of early expressed tRNAs. These m1A-modified early tRNAs enhance translation efficiency, enabling rapid and necessary synthesis of MYC and of a specific group of key functional proteins. The MYC protein then guides the exit of naive T cells from a quiescent state into a proliferative state and promotes rapid T cell expansion after activation. Conditional deletion of the Trmt61a gene in mouse CD4+ T cells causes MYC protein deficiency and cell cycle arrest, disrupts T cell expansion upon cognate antigen stimulation and alleviates colitis in a mouse adoptive transfer colitis model. Our study elucidates for the first time, to our knowledge, the in vivo physiological roles of tRNA-m1A58 modification in T cell-mediated pathogenesis and reveals a new mechanism of tRNA-m1A58-controlled T cell homeostasis and signal-dependent translational control of specific key proteins.

11.
RSC Adv ; 12(37): 24163-24171, 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-36128536

RESUMO

Energetic composites composed of polymeric binders and metallic fuels are widely used in industrial and military fields, and their performance is largely dependent on the combustion process. Fluorinated energetic polymeric binders can facilitate the combustion of metallic fuels such as aluminum particles and enhance the energetic level of the energetic composites. In this report, fluorinated energetic polyurethanes (FPUs) were applied as binders for energetic composites with aluminum nanoparticles (AlNPs). The fluorinated components in the energetic binder could be a uniform dispersion inside the composites, endowing the composites with decent mechanical properties and high combustion rate. Most significantly, compared with the composites without fluorine, FPU/AlNP energetic composites not only showed a remarkably improved combustion efficiency, but also, surprisingly, a dramatic enhancement in the heat of explosion by 91.2%, despite the low content of fluorine. By analyzing the combustion products together with kinetic simulations derived from chemical reaction neural network (CRNN) modelling, a detailed mechanistic understanding of the combustion process was provided, suggesting the importance of synergistic effects brought by the fluorinated and energetic components.

12.
Front Behav Neurosci ; 16: 995614, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36062260

RESUMO

Dysphagia is one of the most common manifestations of stroke, which can affect as many as 50-81% of acute stroke patients. Despite the development of diverse treatment approaches, the precise mechanisms underlying therapeutic efficacy remain controversial. Earlier studies have revealed that the onset of dysphagia is associated with neurological damage. Neuroplasticity-based transcranial magnetic stimulation (TMS), a recently introduced technique, is widely used in the treatment of post-stroke dysphagia (PSD) by increasing changes in neurological pathways through synaptogenesis, reorganization, network strengthening, and inhibition. The main objective of this review is to discuss the effectiveness, mechanisms, potential limitations, and prospects of TMS for clinical application in PSD rehabilitation, with a view to provide a reference for future research and clinical practice.

13.
Front Oncol ; 12: 968202, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059627

RESUMO

Background: Postoperative recurrence impedes the curability of early-stage hepatocellular carcinoma (E-HCC). We aimed to establish a novel recurrence-related pathological prognosticator with artificial intelligence, and investigate the relationship between pathological features and the local immunological microenvironment. Methods: A total of 576 whole-slide images (WSIs) were collected from 547 patients with E-HCC in the Zhongshan cohort, which was randomly divided into a training cohort and a validation cohort. The external validation cohort comprised 147 Tumor Node Metastasis (TNM) stage I patients from The Cancer Genome Atlas (TCGA) database. Six types of HCC tissues were identified by a weakly supervised convolutional neural network. A recurrence-related histological score (HS) was constructed and validated. The correlation between immune microenvironment and HS was evaluated through extensive immunohistochemical data. Results: The overall classification accuracy of HCC tissues was 94.17%. The C-indexes of HS in the training, validation and TCGA cohorts were 0.804, 0.739 and 0.708, respectively. Multivariate analysis showed that the HS (HR= 4.05, 95% CI: 3.40-4.84) was an independent predictor for recurrence-free survival. Patients in HS high-risk group had elevated preoperative alpha-fetoprotein levels, poorer tumor differentiation and a higher proportion of microvascular invasion. The immunohistochemistry data linked the HS to local immune cell infiltration. HS was positively correlated with the expression level of peritumoral CD14+ cells (p= 0.013), and negatively with the intratumoral CD8+ cells (p< 0.001). Conclusions: The study established a novel histological score that predicted short-term and long-term recurrence for E-HCCs using deep learning, which could facilitate clinical decision making in recurrence prediction and management.

14.
Drug Discov Today ; 27(11): 103351, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36096360

RESUMO

DNA-encoded libraries (DELs) allow starting chemical matter to be identified in drug discovery. The volume of experimental data generated also makes DELs an attractive resource for machine learning (ML). ML allows modeling complex relationships between compounds and numerical endpoints, such as the binding to a target measured by DELs. DELs could also empower other areas of drug discovery. Here, we propose that DELs and ML could be combined to model binding to off-targets, enabling better predictive toxicology. With enough data, ML models can make accurate predictions across a vast chemical space, and they can be reused and expanded across projects. Although there are limitations, more general toxicology models could be applied earlier during drug discovery, illuminating safety liabilities at a lower cost.

15.
Thromb Res ; 219: 70-76, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36126565

RESUMO

BACKGROUND: Dual antiplatelet therapy (DAPT) consisting of acetylsalicylic acid and clopidogrel or ticagrelor increased bleeding complications in patients undergoing coronary artery bypass grafting (CABG). We aimed to compare the bleeding risks between patients treated with clopidogrel and ticagrelor preoperatively and investigate the influence of discontinuation of clopidogrel and ticagrelor on bleeding risk in off-pump CABG (OPCABG). METHODS: We conducted a retrospective analysis of patients with DAPT who underwent OPCABG. The propensity score matching was performed given the baseline differences between clopidogrel- and ticagrelor-treated patients. Bleeding was assessed by chest tube drainage volume and universal definition of perioperative bleeding. RESULTS: This study included 836 patients. Five hundred and fifty patients were treated with clopidogrel and 286 patients treated with ticagrelor before surgery. After matching, 275 patients treated with clopidogrel and 275 patients with ticagrelor were included. There were no significant differences in bleeding between clopidogrel and ticagrelor group. Patients who discontinued clopidogrel before surgery <3 d had a higher risk of severe perioperative bleeding compared with those who discontinued ≥5 d (16.4 % vs. 5.0 %, P = 0.045). By contrast, the risk of severe perioperative bleeding was comparable among patients who discontinued ticagrelor for <3 d, ≥3-5 d and ≥5 d preoperatively (16.2 % vs. 9.1 % vs. 10.1 %, P = 0.317). The multivariable analysis confirmed that time since discontinuation (<3 d vs. ≥5 d: OR = 2.732, 95 % CI: 1.332-5.605, P = 0.006) but not the types of P2Y12 receptor antagonist was an independent predictor for severe perioperative bleeding. CONCLUSIONS: There were no significant differences in severe perioperative bleeding between clopidogrel and ticagrelor groups. Discontinuation of clopidogrel <3 d before OPCABG increased the risk of severe perioperative bleeding.

16.
Food Chem ; 402: 134080, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36137383

RESUMO

Multiple emulsions have drawn great attentions from researchers in the production of low-fat foods. The Monascus pigment W/O/W multiple emulsions were prepared by a two-step emulsification procedure with Monascus pigment as inner water phase, flaxseed gum (FG) as internal water phase gel, soybean oil as oil phase, and pea protein isolate (PPI) as outer water phase. We aimed to investigate the quality of pork emulsion systems in which pork fat was replaced by W/O/W emulsions. The results revealed that addition of W/O/W emulsions reduced lipid contents from 11.22% to 5.09%, enhanced protein level from 15.77% to 17.02%, increased polyunsaturated fatty acid composition from 23.36% to 59.63%, improved water-holding capacity and oxidative stability compared to the control samples with pork fat. It was demonstrated that meat systems could achieve dual functions including decreasing the total fat content without affecting the hardness of the meat systems and color retention.

17.
Microbiol Spectr ; : e0207222, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36129287

RESUMO

The emergence and spread of antibiotic resistance pose serious environmental and health challenges. Attention has been drawn to phage therapy as an alternative approach to combat antibiotic resistance with immense potential. However, one of the obstacles to phage therapy is phage resistance, and it can be acquired through genetic mutations, followed by consequences of phenotypic variations. Therefore, understanding the mechanisms underlying phage-host interactions will provide us with greater detail on how to optimize phage therapy. In this study, three lytic phages (phipa2, phipa4, and phipa10) were isolated to investigate phage resistance and the potential fitness trade-offs in Pseudomonas aeruginosa. Specifically, in phage-resistant mutants phipa2-R and phipa4-R, mutations in conferring resistance occurred in genes pilT and pilB, both essential for type IV pili (T4P) biosynthesis. In the phage-resistant mutant phipa10-R, a large chromosomal deletion of ~294 kb, including the hmgA (homogentisate 1,2-dioxygenase) and galU (UTP-glucose-1-phosphate uridylyltransferase) genes, was observed and conferred phage phipa10 resistance. Further, we show examples of associated trade-offs in these phage-resistant mutations, e.g., impaired motility, reduced biofilm formation, and increased antibiotic susceptibility. Collectively, our study sheds light on resistance-mediated genetic mutations and their pleiotropic phenotypes, further emphasizing the impressive complexity and diversity of phage-host interactions and the challenges they pose when controlling bacterial diseases in this important pathogen. IMPORTANCE Battling phage resistance is one of the main challenges faced by phage therapy. To overcome this challenge, detailed information about the mechanisms of phage-host interactions is required to understand the bacterial evolutionary processes. In this study, we identified mutations in key steps of type IV pili (T4P) and O-antigen biosynthesis leading to phage resistance and provided new evidence on how phage predation contributed toward host phenotypes and fitness variations. Together, our results add further fundamental knowledge on phage-host interactions and how they regulate different aspects of Pseudomonas cell behaviors.

18.
Front Immunol ; 13: 961129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110846

RESUMO

Background: Rheumatoid arthritis (RA) is the most common inflammatory arthropathy. Immune dysregulation was implicated in the pathogenesis of RA. Thus, the aim of the research was to determine the immune related biomarkers in RA. Methods: We downloaded the gene expression data of RA in GSE89408 and GSE45291 from Gene Expression Omnibus public database (GEO). Differentially expressed genes (DEGs) were identified between RA and control groups. Infiltrating immune cells related genes were obtained by ssGSEA and weighted gene co-expression network analysis (WGCNA). We performed functional enrichment analysis of differentially expressed immunity-related genes (DEIRGs) by "clusterProfiler" R package, key genes screening by protein-protein interaction (PPI) network of DEIRGs. And mice collagen-induced arthritis (CIA) model was employed to verify these key genes. Results: A total of 1,885 up-regulated and 1,899 down-regulated DEGs were identified in RA samples. The ssGSEA analysis showed that the infiltration of 25 cells was significantly different. 603 immune related genes were obtained by WGCNA, and 270 DEIRGs were obtained by taking the intersection of DEGs and immune related genes. Enrichment analyses indicated that DEIRGs were associated with immunity related biological processes. 4 candidate biomarkers (CCR7, KLRK1, TIGIT and SLAMF1) were identified from the PPI network of DEIRGs and literature research.In mice CIA model, the immunohistochemical stain showed SLAMF1 has a significantly high expression in diseased joints. And flow cytometry analysis shows the expression of SLAMF1 on CIA mice-derived CTL cells, Th, NK cells, NKT cells, classical dendritic cell (cDCs) and monocytes/macrophages was also significantly higher than corresponding immune cells from HC mice. Conclusion: Our study identified SMLAF1 as a key biomarker in the development and progression of RA, which might provide new insight for exploring the pathogenesis of RA.


Assuntos
Artrite Experimental , Artrite Reumatoide , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária , Animais , Artrite Experimental/genética , Artrite Reumatoide/genética , Biomarcadores , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Humanos , Camundongos , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Receptores CCR7/genética , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária/genética
19.
J Fungi (Basel) ; 8(9)2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36135677

RESUMO

In real-time quantitative PCR (RT-qPCR), internal control genes (ICGs) are crucial for normalization. This study screened 6 novel ICGs: Pre-mRNA-splicing factor cwc15 (Cwf15); ER associated DnaJ chaperone (DnaJ); E3 ubiquitin-protein ligase NEDD4 (HUL4); ATP-binding cassette, subfamily B (MDR/TAP), member 1 (VAMP); Exosome complex exonuclease DIS3/RRP44 (RNB); V-type H+-transporting ATPase sub-unit A (V-ATP) from the 22-transcriptome data of 8 filamentous fungi. The six novel ICGs are all involved in the basic biological process of cells and share the different transcription levels from high to low. In order to further verify the stability of ICGs candidates, the six novel ICGs as well as three traditional housekeeping genes: ß-actin (ACTB); ß-tubulin (ß-TUB); glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) and the previously screened reference genes: SPRY-domain-containing protein (SPRYp); Ras-2 protein (Ras); Vacuolar protein sorting protein 26 (Vps26) were evaluated by geNorm and NormFinder statistical algorithms. RT-qPCR of 12 ICGs were performed at different developmental stages in Flammulina filiformis and under different treatment conditions in Neurospora crassa. The consistent results of the two algorithms suggested that the novel genes, RNB, V-ATP, and VAMP, showed the highest stability in F. filiformis and N. crassa. RNB, V-ATP, and VAMP have high expression stability and universal applicability and therefore have great potential as ICGs for standardized calculation in filamentous fungi. The results also provide a novel guidance for the screening stable reference genes in RT-qPCR and a wide application in gene expression analysis of filamentous fungi.

20.
Asian J Androl ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36124533

RESUMO

Urethral plate (UP)-preserving urethroplasty is simple and has few complications, but it may affect the development of penis in the long term and lead to recurrent chordee. In this study, we used obliquely cut UP to repair hypospadias with mild chordee after degloving (15°-30°) and compared the results with onlay urethroplasty to explore its rationality and feasibility. Between April 2018 and October 2020, 108 hypospadias patients underwent onlay urethroplasty or modified onlay urethroplasty. Clinical data were prospectively collected, and medium-term outcomes were assessed at follow-up. The complications were compared between the two groups. Forty-four patients underwent the modified onlay procedure (Group I), with follow-up time (mean ± standard deviation [s.d.]) of 23.2 ± 4.5 (range: 17-31) months. Sixty-four patients underwent a standard onlay procedure (Group II), with follow-up time (mean ± s.d.) of 39.7 ± 3.9 (range: 32-46) months. There was no difference in age at surgery. The urethral defect length and operative time were longer in Group I. Six cases of fistula and one case each of stricture and diverticulum were reported in Group I. In Group II, 11 cases of fistula and one case each of stricture and diverticulum were reported. The complication rates were 18.2% and 20.3% in Group I and Group II, respectively (P > 0.05). These medium-term follow-up results demonstrate that the modified onlay procedure (oblique cut UP urethroplasty) is a safe and feasible technique for hypospadias with mild chordee after degloving. Compared with standard onlay urethroplasty, this modified procedure is conducive to the complete removal of scar tissue underlying the UP without increasing the risk of surgical complications.

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