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1.
J Nanobiotechnology ; 22(1): 586, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39342329

RESUMO

Lymph node metastasis (LNM) is a typical marker in oral squamous cell carcinoma (OSCC) indicating poor prognosis. Pathological examination by artificial image acquisition and analysis, as the main diagnostic method for LNM, often takes a week or longer which may cause great anxiety of the patient and also retard timely treatment. However, there are few efficient fast LNM diagnosis methods in clinical applications currently. Our previous study profiled the proteomics of extracellular vesicles (EVs) derived from postoperative drainage fluid (PDF) and showed the potential of detecting specific EVs that expressed aspartate ß-hydroxylase (ASPH) for LNM diagnosis in OSCC patients. Considering that the analysis of ASPH+ PDF-EVs is challenging due to their low abundance (counting less than 10% of total EVs in PDF) and the complex EV isolation process of ultra-centrifugation, we developed a facile platform containing two microfluidic chips filled with antibody-modified microbeads to isolate ASPH+ PDF-EVs, with both the capture and retrieval rate reaching around 90%. Clinical sample analysis based on our method revealed that a mean of 6 × 106 /mL ASPH+ PDF-EVs could be isolated from LNM+ OSCC patients compared to 2.5 × 106 /mL in LNM- OSCC ones. When combined with enzyme-linked immunosorbent assay (ELISA) technique that was commonly used in clinical laboratories in hospitals, this microfluidic platform could precisely distinguish postoperative OSCC patients with LNM or not in several hours, which were validated by a double-blind test containing 6 OSCC patients. We believe this strategy has promise for early diagnosis of LNM in postoperative OSCC patients and finally helps guiding timely and reasonable treatment in clinic.


Assuntos
Vesículas Extracelulares , Metástase Linfática , Neoplasias Bucais , Humanos , Vesículas Extracelulares/metabolismo , Neoplasias Bucais/cirurgia , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Microfluídica/métodos , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Biomarcadores Tumorais/metabolismo , Feminino , Dispositivos Lab-On-A-Chip , Masculino , Período Pós-Operatório , Pessoa de Meia-Idade , Drenagem/métodos
2.
J Org Chem ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39298438

RESUMO

A highly effective external photocatalyst- and additive-free method for the phosphorylation of 3,4-dihydroquinoxalin-2(1H)-ones to produce phosphorylated dihydroquinoxalin-2(1H)-ones has been reported. A wide variety of phosphorylated products were formed in good to excellent yields. Preliminary mechanistic studies reveal that the phosphorylation process involves an EnT process, a SET process, a HAT process, and a deprotonation process.

3.
Mol Neurobiol ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39271627

RESUMO

"Brain fog," a persistent cognitive impairment syndrome, stands out as a significant neurological aftermath of coronavirus disease 2019 (COVID-19). Yet, the underlying mechanisms by which COVID-19 induces cognitive deficits remain elusive. In our study, we observed an upregulation in the expression of genes linked to the inflammatory response and oxidative stress, whereas genes associated with cognitive function were downregulated in the brains of patients infected with COVID-19. Through single-nucleus RNA sequencing (snRNA-seq) analysis, we found that COVID-19 infection triggers the immune responses in microglia and astrocytes and exacerbates oxidative stress in oligodendrocytes, oligodendrocyte progenitors (OPCs), and neurons. Further investigations revealed that COVID-19 infection elevates LUC7L2 expression, which inhibits mitochondrial oxidative phosphorylation (OXPHOS) and suppresses the expression of mitochondrial complex genes such as MT-ND1, MT-ND2, MT-ND3, MT-ND4L, MT-CYB, MT-CO3, and MT-ATP6. A holistic approach to protect mitochondrial complex function, rather than targeting a single molecular, should be an effective therapeutic strategy to prevent and treat the long-term consequences of "long COVID."

4.
Front Oncol ; 14: 1416888, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39234398

RESUMO

Introduction: Patients with renal insufficiency are more prone to postoperative complications (PCs). Studies have shown that minor changes in serum creatinine (SCr), immediately post-surgery, can aid in assessing patients' renal function. This study aimed to explore the relationship between the changes in SCr and PCs in patients with gastric cancer (GC). Materials and methods: We prospectively collected data regarding the SCr of 530 GC patients, within 2 weeks before surgery and within 24 hours after surgery in our hospital (2014-2016). The patients were divided into three groups according to the level of SCr change after surgery: reduced (<10%), normal (10%), and elevated (>10%) creatinine groups. Univariate and multivariate logistic analysis were performed to evaluate its correlation with short-term PCs in the patients. The R language was used to construct a nomogram. Results: 83, 217, and 230 patients were assigned to the elevated, reduced, and normal SCr groups, respectively. Multivariate analysis showed that the reduced and elevated SCr groups were independently associated with the occurrence of PCs and severe postoperative complications (SPCs), respectively. Additionally, postsurgical SCr change, age, hypoalbuminemia, total gastrectomy, combined resection, and laparoscopy, were independently related to PCs. Combining the above influential factors, the predictive model can distinguish patients with PCs more reliably (c-index is 0.715). Conclusion: Post-surgery, reduced SCr is a protective factor for PCs, while elevated serum creatinine is an independent risk factor for SPCs. Our nomogram can identify GC patients with high risks of PCs.

5.
Front Immunol ; 15: 1450998, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39281670

RESUMO

Programmed cell death (PCD) is a fundamental biological process for maintaining cellular equilibrium and regulating development, health, and disease across all living organisms. Among the various types of PCD, apoptosis plays a pivotal role in numerous diseases, notably cancer. Cancer cells frequently develop mechanisms to evade apoptosis, increasing resistance to standard chemotherapy treatments. This resistance has prompted extensive research into alternative mechanisms of programmed cell death. One such pathway is oncosis, characterized by significant energy consumption, cell swelling, dilation of the endoplasmic reticulum, mitochondrial swelling, and nuclear chromatin aggregation. Recent research suggests that oncosis can impact conditions such as chemotherapeutic cardiotoxicity, myocardial ischemic injury, stroke, and cancer, mediated by specific oncosis-related proteins. In this review, we provide a detailed examination of the morphological and molecular features of oncosis and discuss various natural or small molecule compounds that can induce this type of cell death. Additionally, we summarize the current understanding of the molecular mechanisms underlying oncosis and its role in both normal physiology and pathological conditions. These insights aim to illuminate future research directions and propose innovative strategies for leveraging oncosis as a therapeutic tool against human diseases and cancer resistance.


Assuntos
Apoptose , Neoplasias , Humanos , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias/tratamento farmacológico , Animais , Transdução de Sinais , Morte Celular , Mitocôndrias/metabolismo
6.
Phys Life Rev ; 51: 33-59, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39288541

RESUMO

Parrondo's paradox refers to the paradoxical phenomenon of combining two losing strategies in a certain manner to obtain a winning outcome. It has been applied to uncover unexpected outcomes across various disciplines, particularly at different spatiotemporal scales within ecosystems. In this article, we provide a comprehensive review of recent developments in Parrondo's paradox within the interdisciplinary realm of the physics of life, focusing on its significant applications across biology and the broader life sciences. Specifically, we examine its relevance from genetic pathways and phenotypic regulation, to intercellular interaction within multicellular organisms, and finally to the competition between populations and species in ecosystems. This phenomenon, spanning multiple biological domains and scales, enhances our understanding of the unified characteristics of life and reveals that adaptability in a drastically changing environment, rather than the inherent excellence of a trait, underpins survival in the process of evolution. We conclude by summarizing our findings and discussing future research directions that hold promise for advancing the field.

7.
J Anal Methods Chem ; 2024: 8062001, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39268058

RESUMO

Background: The primary pathogen responsible for bronchoscope contamination is Pseudomonas aeruginosa. Conventional techniques for bronchoscopy disinfection and pathogen identification methods are characterized by time-consuming and operation complexly. The objective of this research is to establish a prompt and precise method for the identification of Pseudomonas aeruginosa, with the ultimate goal of mitigating the risk of nosocomial infections linked to this pathogen. Methods: The magnetic nanoparticles (MNPs) were synthesized in a single step, followed by the optimization of the coating process with antibodies and invertase to produce the bifunctionalized IMIc. Monoclonal antibodies were immobilized on microplates for the specific capture and enrichment of Pseudomonas aeruginosa. Upon the presence of Pseudomonas aeruginosa, the monoclonal antibodies, the test sample, and the IMIc formed sandwich structures. The subsequent addition of a sucrose solution allowed for the detection of glucose produced through invertase hydrolysis by a personal glucose meter, enabling quantitative assessment of Pseudomonas aeruginosa concentration. Results: TEM image demonstrates that the MNPs exhibit a consistent spherical shape. NTA determined that the grain diameter of magnetic nanoparticles was 200 nm. FTIR spectrum revealed the successful modification of two carboxyl groups on the MNPs. The optimization of the incubation pH of the microplate-coated antibody was 7. The optimization of the incubation time of the microplate-coated antibody was 2 h. The optimization of the ligation pH for the polyclonal antibody was 5. Reaction times of polyclonal antibodies linked to magnetic beads was 1 h. The pH of invertase linked by magnetic beads was 4. Conclusion: This article presents a novel qualitative and quantitative immunoassay for point-of-care monitoring of P. aeruginosa utilizing PGM as a readout. The PGM represents a convenient and accurate quantitative detection method suitable for potential clinical diagnostic applications.

8.
Future Oncol ; : 1-8, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39268916

RESUMO

Extremity soft tissue sarcoma (ESTS) is a rare malignant nonepithelial disease, calling for combined modality treatments with surgery to further improve local control rates and long-term survival, especially in patients with multiple local recurrences with or without risk of amputation. In this double-arm, open-label, Phase II clinical trial, we will enroll 30 patients with pathologically confirmed ESTS without nodal involvement or distant metastases. Patients are randomly assigned to the combination treatment group or the radiation monotherapy group. Additionally, tumor and biological samples will be obtained directly before and after neoadjuvant therapy, allowing for studies of immune response and primary drug resistance mechanisms.Clinical Trial Registration: ChiCTR2200060659 (http://www.chictr.org.cn) (ClinicalTrials.gov).


[Box: see text].

9.
Cell Discov ; 10(1): 92, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39223112

RESUMO

Human ABC transporters ABCD1-3 are all localized on the peroxisomal membrane and participate in the ß-oxidation of fatty acyl-CoAs, but they differ from each other in substrate specificity. The transport of branched-chain fatty acids from cytosol to peroxisome is specifically driven by ABCD3, dysfunction of which causes severe liver diseases such as hepatosplenomegaly. Here we report two cryogenic electron microscopy (cryo-EM) structures of ABCD3 bound to phytanoyl-CoA and ATP at resolutions of 2.9 Å and 3.2 Å, respectively. A pair of phytanoyl-CoA molecules were observed in ABCD3, each binding to one transmembrane domain (TMD), which is distinct from our previously reported structure of ABCD1, where each fatty acyl-CoA molecule strongly crosslinks two TMDs. Upon ATP binding, ABCD3 exhibits a conformation that is open towards the peroxisomal matrix, leaving two extra densities corresponding to two CoA molecules deeply embedded in the translocation cavity. Structural analysis combined with substrate-stimulated ATPase activity assays indicated that the present structures might represent two states of ABCD3 in the transport cycle. These findings advance our understanding of fatty acid oxidation and the molecular pathology of related diseases.

10.
Neurol Sci ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39266808

RESUMO

BACKGROUND: Primary Meige syndrome (PMS) is a rare form of dystonia, and comparative analysis of globus pallidus internal deep brain stimulation (GPi-DBS), subthalamic nucleus deep brain stimulation (STN-DBS), and pallidotomy has been lacking. This study aims to compare the efficacy, safety, and psychiatric features of GPi-DBS, STN-DBS, and pallidotomy in patients with PMS. METHODS: This prospective cohort study was divided into three groups: GPi-DBS, STN-DBS, and pallidotomy. Clinical assessments, including motor and non-motor domains, were evaluated at baseline and at 1 year and 3 years after neurostimulation/surgery. RESULTS: Ninety-eight patients were recruited: 46 patients received GPi-DBS, 34 received STN-DBS, and 18 underwent pallidotomy. In the GPi-DBS group, the movement score of the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) improved from a mean (SE) of 13.8 (1.0) before surgery to 5.0 (0.7) (95% CI, -10.5 to -7.1; P < 0.001) at 3 years. Similarly, in the STN-DBS group, the mean (SE) score improved from 13.2 (0.8) to 3.5 (0.5) (95% CI, -10.3 to -8.1; P < 0.001) at 3 years, and in the pallidotomy group, it improved from 14.9 (1.3) to 6.0 (1.1) (95% CI, -11.3 to -6.5; P < 0.001) at 3 years. They were comparable therapeutic approaches for PMS that can improve motor function and quality of life without non-motor side effects. CONCLUSIONS: DBS and pallidotomy are safe and effective treatments for PMS, and an in-depth exploration of non-motor symptoms may be a new entry point for gaining a comprehensive understanding of the pathophysiology.

11.
Langmuir ; 40(37): 19739-19750, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39219094

RESUMO

Depression is a debilitating mental illness that severely threatens millions of individuals and public health. Because of the multifactorial etiologies, there is currently no cure for depression; thus, it is urgently imperative to find alternative antidepressants and strategies. Growing evidence underscores the prominent role of oxidative stress as key pathological hallmarks of depression, making oxidative stress a potential therapeutic target. In this study, we report a N-doped carbon dot nanozyme (CDzyme) with excellent antioxidant capacity for treating depression by remodeling redox homeostasis and gut microbiota. The CDzymes prepared via microwave-assisted fast polymerization of histidine and glucose exhibit superior biocompatibility. Benefiting from the unique structure, CDzymes can provide abundant electrons, hydrogen atoms, and protons for reducing reactions, as well as catalytic sites to mimic redox enzymes. These mechanisms collaborating endow CDzymes with broad-spectrum antioxidant capacity to scavenge reactive oxygen and nitrogen species (•OH, O2-•, H2O2, ONOO-), and oxygen/nitrogen centered free radicals. A depression animal model was established by chronic unpredictable mild stress (CUMS) to evaluate the therapeutic efficacy of CDzymes from the behavioral, physiological, and biochemical index and intestinal flora assessments. CDzymes can remarkably improve depression-like behaviors and key neurotransmitters produced in hippocampus tissues and restore the gut microbiota compositions and the amino acid metabolic functions, proving the potential in treating depression through the intestinal-brain axis system. This study will facilitate the development of intestinal flora dysbiosis nanomedicines and treatment strategies for depression and other oxidative stress related multifactorial diseases.


Assuntos
Antioxidantes , Carbono , Depressão , Microbioma Gastrointestinal , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Carbono/química , Carbono/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Depressão/tratamento farmacológico , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Masculino , Pontos Quânticos/química , Antidepressivos/farmacologia , Antidepressivos/química
12.
Int J Biol Macromol ; 280(Pt 1): 135688, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39288853

RESUMO

Prenyltransferases play a pivotal role in the isoprenoid biosynthesis and transfer in insects. In the current study, two classes of prenyltransferases (MhieFPPS1 and MhieFPPS2, MhiePFT-ß and MhiePF/GGT-α) were identified in the leaf beetle, Monolepta hieroglyphica. Phylogenetic analysis revealed that MhieFPPS1, MhieFPPS2, MhiePFT-ß and MhiePF/GGT-α were clustered in one clade with homologous in insects. Moreover, MhieFPPS2 lacked one aspartate-rich motif SARM. Molecular docking and kinetic analysis indicated that the (E)-GPP displayed higher affinity with MhieFPPS1 compared to DMAPP within the binding pocket containing metal binding sites (MG). The other class of prenyltransferases (MhiePFT-ß and MhiePF/GGT-α) lack the aspartate-rich motif. Docking results indicated that binding site of MhiePFT-ß involved divalent metal ions (Zn) and bound farnesyl or geranylgeranyl. In vitro, only recombiant MhieFPPS1 could catalyze the formation of (E)-farnesol against different combination of substrates, including IPP/DMAPP and IPP/(E)-GPP, highlighting the importance of SARM for enzyme activities. Kinetic analysis further indicated that MhiePFT-ß operated via Zn2+-dependent substrate binding, while MhiePF/GGT-α stabilized the ß-subunit during catalytic reaction. These findings contribute to a valuable insight in to understanding of the mechanisms involved in the biosynthesis and delivery of isoprenoid products in beetles.

13.
Environ Sci Technol ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39321415

RESUMO

While unconventional oil and gas (UOG) development is changing the world economy, processes that are used during UOG development such as high-volume hydraulic fracturing ("fracking") have been linked with water contamination. Water quality risks include leaks of gas and salty fluids (brines) that are coproduced at wellpads. Identifying the cause of contamination is difficult, however, because UOG wells are often colocated with other contaminant sources. We investigated the world's largest shale gas play with publicly accessible groundwater data (Marcellus Shale in Pennsylvania, U.S.A. with ∼29,000 analyses) and discovered that concentrations of brine-associated barium ([Ba]) and strontium ([Sr]) show small regional increases within 1 km of UOG development. Higher concentrations in groundwaters are associated with greater proximity to and density of UOG wells. Concentration increases are even larger when considering associations with the locations of (i) spill-related violations and (ii) some wastewater impoundments. These statistically significant relationships persist even after correcting for other natural and anthropogenic sources of salts. The most likely explanation is that UOG development slightly increases salt concentrations in regional groundwaters not because of fracking but because of the ubiquity of wastewater management issues. These results emphasize the need for stringent wastewater management practices across oil and gas operations.

14.
Genes (Basel) ; 15(9)2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39336816

RESUMO

Background: RT-qPCR is a powerful strategy for recognizing the most appropriate reference genes, which can successfully minimize experimental mistakes through accurate normalization. Ludisia discolor, recognized for its ornamental value, features little, distinctive blossoms with twisted lips and gynostemium showing chiral asymmetry, together with striking blood-red fallen leaves periodically marked with golden blood vessels. Methods and Results: To ensure the accuracy of qRT-PCR, selecting appropriate reference genes for quantifying target gene expression levels is essential. This study aims to identify stable reference genes during the development of L. discolor. In this study, the entire floral buds, including the lips and gynostemium from different development stages, were taken as materials. Based upon the transcriptome information of L. discolor, nine housekeeping genes, ACT, HIS, EF1-α1, EF1-α2, PP2A, UBQ1, UBQ2, UBQ3, and TUB, were selected in this research study as prospect interior referral genes. The expression of these nine genes were found by RT-qPCR and afterwards comprehensively examined by four software options: geNorm, NormFinder, BestKeeper, and ΔCt. The outcomes of the analysis showed that ACT was the most steady gene, which could be the most effective inner referral gene for the expression evaluation of flower advancement in L. discolor. Conclusions: The results of this study will contribute to the molecular biology research of flower development in L. discolor and closely related species.


Assuntos
Flores , Regulação da Expressão Gênica de Plantas , Flores/genética , Flores/crescimento & desenvolvimento , Genes de Plantas , Perfilação da Expressão Gênica/métodos , Genes Essenciais/genética , Padrões de Referência , Reação em Cadeia da Polimerase em Tempo Real/normas , Reação em Cadeia da Polimerase em Tempo Real/métodos , Transcriptoma/genética , Proteínas de Plantas/genética
15.
Phytomedicine ; 134: 155957, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39181101

RESUMO

BACKGROUND: Type 2 diabetes (T2DM) is one of the major metabolic diseases and poses a serious challenge to human life and global economic development. Jinqi Jiangtang Tablets (JQJT) is effective in ameliorating the effects of T2DM, but the mechanism of JQJT is unclear. PURPOSE: This study integrated metabolomics and transcriptomics to reveal the mechanism by which JQJT improves T2DM. METHODS: The T2DM mouse model was established, and the effects of JQJT on improving T2DM were evaluated by determining the levels of blood lipids, fasting blood glucose (FBG), insulin metabolism and hepatic lipid accumulation in mice after JQJT administration for 8 weeks. Serum metabolites were detected using ultra-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry (UPLC-Q-TOF-MS) technology, and mouse liver differential genes were detected using transcriptomic technology. Correlation analysis was used to extract metabolites and RNA with correlations, and potential pathways were enriched and constructed using the common pathway analysis function of MetaboAnalyst 5.0. Finally, the expression of key target proteins and genes was verified by Western blot (WB) and Polymerase Chain Reaction (PCR) to further elucidate the mechanism by which JQJT improves T2DM. RESULTS: JQJT reduced FBG and lipid levels, improved insulin resistance (IR) and hepatic lipoatrophy in mice. A total of 35 differentially abundant metabolites were identified by metabolomics, and 328 differential genes were detected by transcriptomics. The integrated metabolomics and transcriptomics results suggested that JQJT may ameliorate T2DM mainly by regulating glucose and lipid metabolic pathways. WB and PCR results showed that JQJT regulates the insulin signaling pathway, involved in fatty acid metabolism, glycogen synthesis and catabolism. CONCLUSIONS: JQJT improved IR in T2DM mice by regulating the insulin signaling pathway, improving glycogen synthesis and glycolysis, and increasing hepatic triglyceride and fatty acid metabolism.


Assuntos
Glicemia , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Fígado , Metabolômica , Animais , Medicamentos de Ervas Chinesas/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Camundongos , Glicemia/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Insulina/sangue , Insulina/metabolismo , Comprimidos , Transcriptoma/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Perfilação da Expressão Gênica , Lipídeos/sangue
16.
Poult Sci ; 103(10): 104068, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39096825

RESUMO

Avian influenza virus (AIV) subtype H9N2 has significantly threatened the poultry business in recent years by having become the predominant subtype in flocks of chickens, ducks, and pigeons. In addition, the public health aspects of H9N2 AIV pose a significant threat to humans. Early and rapid diagnosis of H9N2 AIV is therefore of great importance. In this study, a new method for the detection of H9N2 AIV based on fluorescence intensity was successfully established using CRISPR/Cas13a technology. The Cas13a protein was first expressed in a prokaryotic system and purified using nickel ion affinity chromatography, resulting in a high-purity Cas13a protein. The best RPA (recombinase polymerase amplification) primer pairs and crRNA were designed and screened, successfully constructing the detection of H9N2 AIV based on CRISPR/Cas13a technology. Optimal concentration of Cas13a and crRNA was determined to optimize the constructed assay. The sensitivity of the optimized detection system is excellent, with a minimum detection limit of 10° copies/µL and didn't react with other avian susceptible viruses, with excellent specificity. The detection method provides the basis for the field detection of the H9N2 AIV.


Assuntos
Sistemas CRISPR-Cas , Galinhas , Edição de Genes , Vírus da Influenza A Subtipo H9N2 , Influenza Aviária , Doenças das Aves Domésticas , Vírus da Influenza A Subtipo H9N2/genética , Vírus da Influenza A Subtipo H9N2/isolamento & purificação , Influenza Aviária/virologia , Influenza Aviária/diagnóstico , Animais , Edição de Genes/métodos , Edição de Genes/veterinária , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/diagnóstico , Patos
17.
J Immunol ; 213(7): 1008-1022, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39194407

RESUMO

The functions of the natural dsRNA sensors TLR3 (TRIF) and RIG-I (MAVS) are crucial during viral challenge and have not been accurately clarified in adaptive immune responses to rotavirus (RV) infection. In this study, we found that RV infection caused severe pathological damage to the small intestine of TLR3-/- and TRIF-/- mice. Our data found that dendritic cells from TLR3-/- and TRIF-/- mice had impaired Ag presentation to the RV and attenuated initiation of T cells upon viral infection. These attenuated functions resulted in impaired CD4+ T and CD8+ T function in mice lacking TLR3-TRIF signaling postinfection. Additionally, attenuated proliferative capacity of T cells from TLR3-/- and TRIF-/- mice was observed. Subsequently, we observed a significant reduction in the absolute number of memory T cells in the spleen and mesenteric lymph node (MLN) of TRIF-/- recipient mice following RV infection in a bone marrow chimeric model. Furthermore, there was reduced migration of type 2 classical dendritic cells from the intestine to MLNs after RV infection in TLR3-/- and TRIF-/- mice. Notably, RV infection resulted in attenuated killing of spleen and MLN tissues in TRIF-/- and MAVS-/- mice. Finally, we demonstrated that RV infection promoted apoptosis of CD8+ T cells in TRIF-/- and TLR3-/-MAVS-/- mice. Taken together, our findings highlight an important mechanism of TLR3 signaling through TRIF in mucosal T cell responses to RV and lay the foundation for the development of a novel vaccine.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas Adaptadoras de Transporte Vesicular , Células Dendríticas , Camundongos Knockout , Infecções por Rotavirus , Rotavirus , Transdução de Sinais , Receptor 3 Toll-Like , Animais , Receptor 3 Toll-Like/imunologia , Camundongos , Infecções por Rotavirus/imunologia , Transdução de Sinais/imunologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Rotavirus/imunologia , Células Dendríticas/imunologia , Camundongos Endogâmicos C57BL , Mucosa Intestinal/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunidade nas Mucosas , Apresentação de Antígeno/imunologia
18.
Ann Med ; 56(1): 2387302, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39101236

RESUMO

BACKGROUND: Cushing's syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters. METHODS: A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD. RESULTS: A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p < 0.001). CS patients had noticeably increased visceral fat but decreased skeletal muscle in comparison to their healthy counterparts. Higher prevalence of LVDD was found in CS patients based on LV diastolic function evaluated by E/A ratio (p < 0.001). EATV was proved to be an independent risk factor for LVDD in CS patients (OR = 1.015, 95%CI 1.003-1.026, p = 0.011). If the cut-point of EATV was set as 139.252 cm3 in CS patients, the diagnostic sensitivity and specificity of LVDD were 84.00% and 55.60%, respectively. CONCLUSION: CS was associated with marked accumulation of EAT and visceral fat, reduced skeletal muscle mass, and increased prevalence of LVDD. EATV was an independent risk factor for LVDD, suggesting the potential role of EAT in the development of LVDD in CS.


This study explored the potential risk factors of LVDD in endogenous CS by incorporating body composition parameters. EATV was identified as an independent risk factor for LVDD. Targeted therapeutic interventions to reduce excessive cortisol-induced EAT accumulation may be promising to mitigate the risk of LVDD development in patients with CS.


Assuntos
Tecido Adiposo , Síndrome de Cushing , Ecocardiografia , Pericárdio , Disfunção Ventricular Esquerda , Humanos , Masculino , Síndrome de Cushing/fisiopatologia , Síndrome de Cushing/complicações , Síndrome de Cushing/epidemiologia , Feminino , Estudos Retrospectivos , Adulto , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Esquerda/etiologia , Pericárdio/diagnóstico por imagem , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/fisiopatologia , Pessoa de Meia-Idade , Diástole , Fatores de Risco , Estudos de Casos e Controles , Tomografia Computadorizada por Raios X , Tecido Adiposo Epicárdico
19.
J Surg Res ; 302: 240-249, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39111127

RESUMO

INTRODUCTION: The risk of surgery and postoperative complications increases greatly in frail older patients with sarcopenia. The purpose of this study is to explore the correlation between myostatin (MSTN) levels and cognitive function and postoperative pulmonary complications (PPCs) in older patients undergoing thoracoscopic lobectomy and to determine whether MSTN could be used to predict the risk of postoperative complications and cognitive impairment. METHODS: A prospective observational study was conducted at the First Affiliated Hospital of Bengbu Medical College, China, between January 2023 and June 2023. The risk factors of PPCs and postoperative cognitive impairment were studied using backward stepwise logistic regression analysis. The independent factors were formed into a linear regression equation to construct a risk score model for each patient. The 122 patients who participated in the study were divided into two groups, a low-level group and a high-level group, based on an MSTN level cut-off; the preoperative MSTN cut-off values was 25.55 ng/mL for cognitive dysfunction and 22.29 ng/mL for PPCs. The PPCs and cognitive function of the groups were compared. RESULTS: Preoperative MSTN was confirmed as a risk factor for postoperative cognitive dysfunction and PPCs. After surgery, the proportion of patients with cognitive impairment in the high-level group was significantly higher than in the low-level group (P < 0.001). In the high-level group, the incidence of respiratory tract infections was 17.9% higher (P = 0.021), hypoxaemia was 20.5% higher (P = 0.001) and respiratory failure was 14.4% higher (P = 0.012) than in the low-level group. In addition, a high level of MSTN increased the length of hospital stay (P < 0.001) and decreased the Barthel Index score (P < 0.001). CONCLUSIONS: The study findings suggest that MSTN could be used as an index to predict complications and cognitive impairment after thoracoscopic lobectomy in older patients with sarcopenia and to provide evidence for reducing postoperative cognitive impairment and PPCs.

20.
Virol J ; 21(1): 183, 2024 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-39129001

RESUMO

BACKGROUNDS: Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen causing respiratory diseases in children. This study aimed to characterize epidemiological and disease severity shifts of M. pneumoniae: infections in Guangzhou, China during and after the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Throat swab samples were obtained from 5405 hospitalized patients with symptoms of acute respiratory infections to detect M. pneumoniae. Differences in epidemiological and clinical characteristics of M. pneumoniae: infections were investigated during 2020-2022 and after COVID-19 pandemic (2023). RESULTS: M. pneumoniae were detected in 849 (15.6%, 849/5405) patients. The highest annual positive rate was 29.4% (754/2570) in 2023, followed by 5.3% (72/1367) in 2022, 1.2% (12/1015) in 2021, and 2.0% (11/553) in 2020, with significantly increasing annual prevalence from 2020 to 2023. M. pneumoniae incidence peaked between July and December post-COVID-19 pandemic in 2023, with the highest monthly positive rate (56.4%, 165/293). Clinical characteristics and outcomes of patients with M. pneumoniae did not vary between periods during and after COVID-19 pandemic except that patients with M. pneumoniae post-COVID-19 pandemic were more likely to develop fever. Patients with severe M. pneumoniae pneumonia (SMPP) were more likely to develop respiratory complications, myocardial damage, and gastrointestinal dysfunction than those with non-SMPP. Patients with SMPP had lower lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and higher IL-4, IL-6, IL-10 levels than those with non-SMPP. Bronchoalveolar lavage fluid specimens from infected patients were obtained to identify macrolide resistance mutations. Macrolide-resistant M. pneumoniae (MRMP) proportion in 2023 was 91.1% (215/236). CONCLUSION: Outbreaks of M. pneumoniae: occurred in Guangzhou, China in 2023 upon Non-pharmaceutical interventions easing. Despite the increasing incidence of M. pneumoniae, the disease severity remained similar during and after the COVID-19 pandemic.


Assuntos
COVID-19 , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Humanos , China/epidemiologia , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/microbiologia , COVID-19/epidemiologia , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/isolamento & purificação , Masculino , Feminino , Criança , Adulto , Adolescente , Pessoa de Meia-Idade , Pré-Escolar , Adulto Jovem , Surtos de Doenças , SARS-CoV-2/genética , Lactente , Idoso , Incidência , Prevalência , Pandemias
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