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1.
Immunity ; 57(9): 2157-2172.e7, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39079536

RESUMO

Stroke leads to persistently high risk for recurrent vascular events caused by systemic atheroprogression that is driven by endothelial cell (EC) activation. However, whether and how stroke induces sustained pro-inflammatory and proatherogenic endothelial alterations in systemic vessels remain poorly understood. We showed that brain ischemia induces persistent activation, the upregulation of adhesion molecule VCAM1, and increased senescence in peripheral ECs until 4 weeks after stroke onset. This aberrant EC activity resulted from sustained Notch1 signaling, which was triggered by increased circulating Notch1 ligands DLL1 and Jagged1 after stroke in mice and humans. Consequently, this led to increased myeloid cell adhesion and atheroprogression by generating a senescent, pro-inflammatory endothelium. Notch1- or VCAM1-blocking antibodies and the genetic ablation of endothelial Notch1 reduced atheroprogression after stroke. Our findings revealed a systemic machinery that induces the persistent activation of peripheral ECs after stroke, which paves the way for therapeutic interventions or the prevention of recurrent vascular events following stroke.


Assuntos
Aterosclerose , Isquemia Encefálica , Proteínas de Ligação ao Cálcio , Células Endoteliais , Receptor Notch1 , Animais , Humanos , Masculino , Camundongos , Aterosclerose/metabolismo , Aterosclerose/imunologia , Isquemia Encefálica/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Adesão Celular , Senescência Celular , Células Endoteliais/metabolismo , Proteína Jagged-1/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor Notch1/metabolismo , Transdução de Sinais , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/imunologia , Molécula 1 de Adesão de Célula Vascular/metabolismo
2.
Genes Dev ; 35(13-14): 1035-1054, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34168040

RESUMO

G9a is a histone methyltransferase responsible for the dimethylation of histone H3 at lysine 9 (H3K9me2). G9a plays key roles in transcriptional silencing of developmentally regulated genes, but its role in X-chromosome inactivation (XCI) has been under debate. Here, we uncover a female-specific function of G9a and demonstrate that deleting G9a has a disproportionate impact on the X chromosome relative to the rest of the genome. G9a deficiency causes a failure of XCI and female-specific hypersensitivity to drug inhibition of H3K9me2. We show that G9a interacts with Tsix and Xist RNAs, and that competitive inhibition of the G9a-RNA interaction recapitulates the XCI defect. During XCI, Xist recruits G9a to silence X-linked genes on the future inactive X. In parallel on the future Xa, Tsix recruits G9a to silence Xist in cis Thus, RNA tethers G9a for allele-specific targeting of the H3K9me2 modification and the G9a-RNA interaction is essential for XCI.


Assuntos
Cromossomos Humanos X , Antígenos de Histocompatibilidade/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Metiltransferases , RNA Longo não Codificante , Feminino , Histonas/metabolismo , Humanos , Metiltransferases/genética , RNA Longo não Codificante/genética , Inativação do Cromossomo X/genética
3.
PLoS Pathog ; 19(2): e1011189, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36812247

RESUMO

Increasing evidence highlights the role of bacteria in promoting tumorigenesis. The underlying mechanisms may be diverse and remain poorly understood. Here, we report that Salmonella infection leads to extensive de/acetylation changes in host cell proteins. The acetylation of mammalian cell division cycle 42 (CDC42), a member of the Rho family of GTPases involved in many crucial signaling pathways in cancer cells, is drastically reduced after bacterial infection. CDC42 is deacetylated by SIRT2 and acetylated by p300/CBP. Non-acetylated CDC42 at lysine 153 shows an impaired binding of its downstream effector PAK4 and an attenuated phosphorylation of p38 and JNK, consequently reduces cell apoptosis. The reduction in K153 acetylation also enhances the migration and invasion ability of colon cancer cells. The low level of K153 acetylation in patients with colorectal cancer (CRC) predicts a poor prognosis. Taken together, our findings suggest a new mechanism of bacterial infection-induced promotion of colorectal tumorigenesis by modulation of the CDC42-PAK axis through manipulation of CDC42 acetylation.


Assuntos
Neoplasias Colorretais , Infecções por Salmonella , Proteína cdc42 de Ligação ao GTP , Humanos , Acetilação , Carcinogênese , Proteína cdc42 de Ligação ao GTP/metabolismo , Transformação Celular Neoplásica , Quinases Ativadas por p21/metabolismo , Transdução de Sinais
4.
Nucleic Acids Res ; 51(19): 10411-10427, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37742082

RESUMO

Acetylation is a global post-translational modification that regulates various cellular processes. Bacterial acetylomic studies have revealed extensive acetylation of ribosomal proteins. However, the role of acetylation in regulating ribosome function remains poorly understood. In this study, we systematically profiled ribosomal protein acetylation and identified a total of 289 acetylated lysine residues in 52 ribosomal proteins (r-proteins) from Salmonella Typhimurium. The majority of acetylated lysine residues of r-proteins were found to be regulated by both acetyltransferase Pat and metabolic intermediate acetyl phosphate. Our results show that acetylation plays a critical role in the assembly of the mature 70S ribosome complex by modulating r-proteins binding to rRNA. Moreover, appropriate acetylation is important for the interactions between elongation factors and polysomes, as well as regulating ribosome translation efficiency and fidelity. Dysregulation of acetylation could alter bacterial sensitivity to ribosome-targeting antibiotics. Collectively, our data suggest that the acetylation homeostasis of ribosomes is crucial for their assembly and function. Furthermore, this mechanism may represent a universal response to environmental signals across different cell types.


Assuntos
Processamento de Proteína Pós-Traducional , Proteínas Ribossômicas , Salmonella typhimurium , Acetilação , Homeostase , Lisina/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Salmonella typhimurium/metabolismo
5.
Proc Natl Acad Sci U S A ; 119(12): e2116776119, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35294289

RESUMO

Shigella flexneri, a gram-negative bacterium, is the major culprit of bacterial shigellosis and causes a large number of human infection cases and deaths worldwide annually. For evading the host immune response during infection, S. flexneri secrets two highly similar E3 ligases, IpaH1.4 and IpaH2.5, to subvert the linear ubiquitin chain assembly complex (LUBAC) of host cells, which is composed of HOIP, HOIL-1L, and SHARPIN. However, the detailed molecular mechanism underpinning the subversion of the LUBAC by IpaH1.4/2.5 remains elusive. Here, we demonstrated that IpaH1.4 can specifically recognize HOIP and HOIL-1L through its leucine-rich repeat (LRR) domain by binding to the HOIP RING1 domain and HOIL-1L ubiquitin-like (UBL) domain, respectively. The determined crystal structures of IpaH1.4 LRR/HOIP RING1, IpaH1.4 LRR/HOIL-1L UBL, and HOIP RING1/UBE2L3 complexes not only elucidate the binding mechanisms of IpaH1.4 with HOIP and HOIL-1L but also unveil that the recognition of HOIP by IpaH1.4 can inhibit the E2 binding of HOIP. Furthermore, we demonstrated that the interaction of IpaH1.4 LRR with HOIP RING1 or HOIL-1L UBL is essential for the ubiquitination of HOIP or HOIL-1L in vitro as well as the suppression of NF-κB activation by IpaH1.4 in cells. In summary, our work elucidated that in addition to inducing the proteasomal degradation of LUBAC, IpaH1.4 can also inhibit the E3 activity of LUBAC by blocking its E2 loading and/or disturbing its stability, thereby providing a paradigm showing how a bacterial E3 ligase adopts multiple tactics to subvert the key LUBAC of host cells.


Assuntos
Shigella flexneri , Ubiquitina-Proteína Ligases , Humanos , NF-kappa B/metabolismo , Shigella flexneri/genética , Shigella flexneri/metabolismo , Transdução de Sinais , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
6.
J Neurosci ; 43(42): 7016-7027, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37696666

RESUMO

White matter of the human brain is influenced by common genetic variations and shaped by neural activity-dependent experiences. Variations in microstructure of cerebral white matter across individuals and even across fiber tracts might underlie differences in cognitive capacity and vulnerabilities to mental disorders. The frontoparietal and cingulo-opercular networks of the brain constitute the central system supporting cognitive functions, and functional connectivity of these networks has been used to distinguish individuals known as "functional fingerprinting." The frontal aslant tract (FAT) that passes through the two networks has been implicated in executive functions. However, whether FAT can be used as a "structural fingerprint" to distinguish individuals and predict an individual's cognitive function and dysfunction is unknown. Here we investigated the fingerprinting property of FAT microstructural profiles using three independent diffusion MRI datasets with repeated scans on human participants including both females and males. We found that diffusion and geometric profiles of FAT can be used to distinguish individuals with a high accuracy. Next, we demonstrated that fractional anisotropy in different FAT segments predicted distinct cognitive functions, including working memory, inhibitory control, and relational reasoning. Finally, we assessed the contribution of altered FAT microstructural profiles to cognitive dysfunction in unmedicated patients with obsessive-compulsive disorders. We found that the altered microstructure in FAT was associated with the severity of obsessive-compulsive symptoms. Collectively, our findings suggest that the microstructural profiles of FAT can identify individuals with a high accuracy and may serve as an imaging marker for predicting an individual's cognitive capacity and disease severity.SIGNIFICANCE STATEMENT The frontoparietal network and cingulo-opercular network of the brain constitute a dual-network architecture for human cognitive functions, and functional connectivity of these two networks can be used as a "functional fingerprint" to distinguish individuals. However, the structural underpinnings of these networks subserving individual heterogeneities in their functional connectivity and cognitive ability remain unknown. We show here that the frontal aslant tract (FAT) that passes through the two networks distinguishes individuals with a high accuracy. Further, we demonstrate that the diffusion profiles of FAT predict distinct cognitive functions in healthy subjects and are associated with the clinical symptoms in patients with obsessive-compulsive disorders. Our findings suggest that the FAT may serve as a unique structural fingerprint underlying individual cognitive capability.


Assuntos
Encéfalo , Transtorno Obsessivo-Compulsivo , Masculino , Feminino , Humanos , Imagem de Difusão por Ressonância Magnética , Cognição , Função Executiva , Transtorno Obsessivo-Compulsivo/diagnóstico , Imageamento por Ressonância Magnética
7.
Biochem Biophys Res Commun ; 703: 149614, 2024 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-38359611

RESUMO

Bone repair strategies, based on endogenous stem cell recruitment, can effectively avoid immune rejection and the low utilization of exogenous stem cells. Endogenous stem cells can be recruited to the implantation site by loading chemokines onto bone tissue-engineered scaffolds. However, challenges such as unstable chemokine activity and easy inactivation after implantation remain significant. In the present study, composite fiber scaffolds ((IL8@LIP)-GelMA) consisting of Interleukin 8 (IL8) -loaded liposomes and GelMA were constructed by electrospinning and photocrosslinking, and its ability to recruit bone marrow-derived mesenchymal stem cells (BMSCs) and immunomodulatory effect was investigated. Compared to GelMA loaded directly with IL8, scaffolds of (IL8@LIP)-GelMA demonstrated superior protection of IL8 activity, ensuring a slow and continuous release. Both in vivo and in vitro experiments demonstrated that the (IL8@LIP)-GelMA scaffolds effectively recruited BMSCs to the desired sites. Additionally, the (IL8@LIP)-GelMA scaffolds exhibited the capacity to recruit more macrophages to the implantation site. Importantly, they promoted the polarization of macrophages toward the M2 anti-inflammatory phenotype, facilitating the transition from the inflammatory stage to the tissue repair stage. Therefore, (IL8@LIP)-GelMA scaffolds show great potential for cell-free tissue engineering applications and provide insights into the loading mode of growth factors in scaffolds.


Assuntos
Interleucina-8 , Lipossomos , Alicerces Teciduais , Engenharia Tecidual , Osso e Ossos , Osteogênese
8.
Small ; : e2403642, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39113658

RESUMO

Potassium metal batteries (PMBs) are promising candidates for large-scale energy storage. Conventional carbonate electrolytes exhibit unsatisfactory thermodynamic stability against potassium (K) metal anode. Linear ether is widely adopted because of its compatibility with K metal, but the poor oxidation stability restricts the application with high-voltage cathodes. Herein, a weakly solvating cyclic ether is proposed as a solvent to stabilize the K-electrolyte interface and build a robust solid-electrolyte interphase (SEI). This weakly solvating electrolyte (WSE) possesses an anion-dominated solvation structure, which facilitates the anion decomposition for constructing an inorganic-rich SEI. The superior mechanical properties of the SEI, as examined by atomic force microscopy, prevent the SEI from fracture. Consequently, this WSE achieves highly reversible plating/stripping behavior of K metal for 1300 h with a high average Coulombic efficiency of 99.20%. Stable full cells are also demonstrated with a high-voltage cathode at harsh conditions. This work complements the design of WSEs for advanced PMBs by cyclic ether solvents.

9.
Yeast ; 41(6): 369-378, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38613186

RESUMO

Engineering Yarrowia lipolytica to produce astaxanthin provides a promising route. Here, Y. lipolytica M2 producing a titer of 181 mg/L astaxanthin was isolated by iterative atmospheric and room-temperature plasma mutagenesis and diphenylamine-mediated screening. Interestingly, a negative correlation was observed between cell biomass and astaxanthin production. To reveal the underlying mechanism, RNA-seq analysis of transcriptional changes was performed in high producer M2 and reference strain M1, and a total of 1379 differentially expressed genes were obtained. Data analysis revealed that carbon flux was elevated through lipid metabolism, acetyl-CoA and mevalonate supply, but restrained through central carbon metabolism in strain M2. Moreover, upregulation of other pathways such as ATP-binding cassette transporter and thiamine pyrophosphate possibly provided more cofactors for carotenoid hydroxylase and relieved cell membrane stress caused by astaxanthin insertion. These results suggest that balancing cell growth and astaxanthin production may be important to promote efficient biosynthesis of astaxanthin in Y. lipolytica.


Assuntos
Perfilação da Expressão Gênica , Xantofilas , Yarrowia , Yarrowia/genética , Yarrowia/metabolismo , Xantofilas/metabolismo , Engenharia Metabólica , Transcriptoma , Regulação Fúngica da Expressão Gênica , Redes e Vias Metabólicas/genética , Análise do Fluxo Metabólico , Metabolismo dos Lipídeos , Biomassa
10.
J Transl Med ; 22(1): 593, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918793

RESUMO

BACKGROUND: Sorafenib resistance is becoming increasingly common and disadvantageous for hepatocellular carcinoma (HCC) treatment. Ferroptosis is an iron dependent programmed cell death underlying the mechanism of sorafenib. Iron is crucial for synthesis of cofactors essential to mitochondrial enzymes and necessary for HCC proliferation, while mitochondrial iron overload and oxidative stress are associated with sorafenib induced ferroptosis. However, the crosstalk among iron homeostasis and sorafenib resistance is unclear. METHODS: We conducted bioinformatics analysis of sorafenib treated HCC datasets to analyze GCN5L1 and iron related gene expression with sorafenib resistance. GCN5L1 deleted HCC cell lines were generated by CRISPR technology. Sorafenib resistant HCC cell line was established to validate dataset analysis and evaluate the effect of potential target. RESULTS: We identified GCN5L1, a regulator of mitochondrial acetylation, as a modulator in sorafenib-induced ferroptosis via affecting mitochondrial iron homeostasis. GCN5L1 deficiency significantly increased sorafenib sensitivity in HCC cells by down-regulating mitochondrial iron transporters CISD1 expression to induce iron accumulation. Mitochondrial iron accumulation leads to an acceleration in cellular and lipid ROS. Sorafenib resistance is related to CISD1 overexpression to release mitochondrial iron and maintaining mitochondrial homeostasis. We combined CISD1 inhibitor NL-1 with sorafenib, which significantly enhanced sorafenib-induced ferroptosis by promoting mitochondrial iron accumulation and lipid peroxidation. The combination of NL-1 with sorafenib enhanced sorafenib efficacy in vitro and in vivo. CONCLUSIONS: Our findings demonstrate that GCN5L1/CISD1 axis is crucial for sorafenib resistance and would be a potential therapeutic strategy for sorafenib resistant HCC.


Assuntos
Carcinoma Hepatocelular , Resistencia a Medicamentos Antineoplásicos , Ferroptose , Homeostase , Ferro , Neoplasias Hepáticas , Mitocôndrias , Sorafenibe , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamento farmacológico , Ferro/metabolismo , Humanos , Homeostase/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Linhagem Celular Tumoral , Animais , Ferroptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Camundongos Nus , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
11.
J Exp Bot ; 75(10): 3171-3187, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38400756

RESUMO

Salt stress is a common abiotic factor that restricts plant growth and development. As a halophyte, Tamarix hispida is a good model plant for exploring salt-tolerance genes and regulatory mechanisms. DNA-binding with one finger (DOF) is an important transcription factor (TF) that influences and controls various signaling substances involved in diverse biological processes related to plant growth and development, but the regulatory mechanisms of DOF TFs in response to salt stress are largely unknown in T. hispida. In the present study, a newly identified Dof gene, ThDOF8, was cloned from T. hispida, and its expression was found to be induced by salt stress. Transient overexpression of ThDOF8 enhanced T. hispida salt tolerance by enhancing proline levels, and increasing the activities of the antioxidant enzymes superoxide dismutase (SOD) and peroxidase (POD). These results were also verified in stably transformed Arabidopsis. Results from TF-centered yeast one-hybrid (Y1H) assays and EMSAs showed that ThDOF8 binds to a newly identified cis-element (TGCG). Expression profiling by gene chip analysis identified four potential direct targets of ThDOF8, namely the cysteine-rich receptor-like kinases genes, CRK10 and CRK26, and two glutamate decarboxylase genes, GAD41, and GAD42, and these were further verified by ChIP-quantitative-PCR, EMSAs, Y1H assays, and ß-glucuronidase enzyme activity assays. ThDOF8 can bind to the TGCG element in the promoter regions of its target genes, and transient overexpression of ThCRK10 also enhanced T. hispida salt tolerance. On the basis of our results, we propose a new regulatory mechanism model, in which ThDOF8 binds to the TGCG cis-element in the promoter of the target gene CRK10 to regulate its expression and improve salt tolerance in T. hispida. This study provides a basis for furthering our understanding the role of DOF TFs and identifying other downstream candidate genes that have the potential for improving plant salt tolerance via molecular breeding.


Assuntos
Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Tamaricaceae , Fatores de Transcrição , Tamaricaceae/genética , Tamaricaceae/metabolismo , Tamaricaceae/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Estresse Salino/genética , Tolerância ao Sal/genética
12.
Reprod Biomed Online ; 49(6): 104326, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-39389002

RESUMO

RESEARCH QUESTION: Does LncRNA BANCR promote the malignant transformation of endometriosis by activating the miR-612/CPNE3 pathway? DESIGN: The expression patterns of BANCR, miR-612 and CPNE3 in normal endometrium, eutopic endometrium from endometriosis, eutopic endometrium or malignant tissues from endometriosis-associated ovarian cancer. On the basis of primary normal endometrial stromal cells (NESC) and eutopic endometrial stromal cells (EESC), the regulatory relationships between BANCR, miR-612 and CPNE3, and the potential mechanisms that promote the malignant transformation of endometriosis, were elucidated in vitro and in vivo. RESULTS: The expression levels of BANCR and CPNE3 were lowest in normal endometrium, significantly increased in eutopic endometrium (P < 0.05) and was significantly increased in eutopic endometrium (P < 0.05). During the malignant transformation of endometriosis, the expression levels of BANCR and CPNE3 were significantly upregulated (P < 0.05), whereas those of miR-612 were significantly downregulated (P < 0.05). miRNA-612 was found to target BANCR and CPNE3. The overexpression and knockdown of BANCR in NESC and EESC upregulated and downregulated the expression of CPNE3 and promoted or prevented cell proliferation and migration, respectively; these effects were reversed by miR-612 mimics and inhibitor. These changes were all statistically significant (P < 0.05). In-vivo experiments revealed that BANCR significantly increased the survival of subcutaneous endometrial cells by regulating miR-612/CPNE3 (P < 0.05). CONCLUSION: The expression of BANCR gradually increased with the progression of endometriosis during malignant transformation, and promoted the proliferation and migration of endometrial cells via the miR-612/CPNE3 pathway. BANCR may represent a novel target for monitoring the malignant transformation of endometriosis.

13.
Parasite Immunol ; 46(2): e13022, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38384176

RESUMO

Chicken coccidiosis, caused by Eimeria protozoa, affects poultry farming. Toll-like receptors (TLRs) and host defence peptides (HDPs) help host innate immune responses to eliminate invading pathogens, but their roles in Eimeria tenella infection remain poorly understood. Herein, 14-day-old chickens were treated orally with 50,000 E. tenella oocysts and the cecum was dissected at different timepoints. mRNA expression of 10 chicken TLRs (chTLRs) and five HDPs was measured by quantitative real-time PCR. chTLR7 and chTLR15 were upregulated significantly at 3 h post-infection while other chTLRs were downregulated (p < .05). chTLR1a, chTLR1b, chTLR2b and chTLR4 peaked at 36 h post-infection, chTLR3, chTLR5 and chTLR15 peaked at 72 h post-infection and chTLR21 expression was highest among chTLRs, peaking at 48 h post-infection (p < 0.05). For HDPs, cathelicidin (CATH) 1 to 3 and B1 peaked at 48 h post-infection, liver-expressed antimicrobial peptide 2 peaked at 96 h post-infection, and CATH 2 expression was highest among HDPs. CATH2 and CATH3 were markedly upregulated at 3 h post-infection (p < .05). The results provide insight into innate immune molecules during E. tenella infection in chicken, and indicate that innate immune responses may mediate resistance to chicken coccidiosis.


Assuntos
Coccidiose , Eimeria tenella , Doenças das Aves Domésticas , Animais , Eimeria tenella/genética , Galinhas/parasitologia , Peptídeos Catiônicos Antimicrobianos/genética , Receptores Toll-Like/genética , Coccidiose/parasitologia , Ceco/parasitologia
14.
Scand J Gastroenterol ; 59(4): 480-488, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38179969

RESUMO

Objective: To examine the impact of moderate alcohol consumption on the progression of chronic kidney disease (CKD) in individuals diagnosed with non-alcoholic fatty liver disease (NAFLD), as NAFLD has been identified as an autonomous risk factor for CKD and previous research has demonstrated a reduction in overall mortality in NAFLD patients who consume alcohol in moderation.Methods: This study included participants from ten consecutive rounds of the National Health and Nutrition Examination Survey (NHANES:1998-2018). Multivariate logistic regression models were employed to assess the impact of moderate alcohol consumption on chronic kidney disease (CKD) in both male and female populations. Subgroup analysis was conducted by categorizing patients with non-alcoholic fatty liver disease (NAFLD) based on the Fibrosis-4 (FIB-4) index.Results: 17040 participants were eligible to be included in the study. The logistic regression analysis model showed that moderate alcohol consumption was a protective factor for CKD in male NAFLD patients, with an unadjusted OR: 0.37 (0.22,0.65), and p < 0.001. After further adjustment, the association persisted. However, the association was not significant in female patients with NAFLD. Among men with low risk of liver fibrosis group, moderate alcohol consumption remained a protective factor for CKD (OR = 0.32, 95% CI 0.12-0.84, p = 0.02), but the association was not significant in the high risk of liver fibrosis group. In female patients, both moderate alcohol consumption and excessive alcohol consumption were not significantly associated with CKD in either the low-risk group or the high-risk group.Conclusion: Moderate alcohol consumption is associated with a lower prevalence of CKD in men with NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Inquéritos Nutricionais , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Cirrose Hepática/complicações
15.
Anal Bioanal Chem ; 416(20): 4491-4501, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38877148

RESUMO

In the present study, click chemistry and Schiff base reactions were simultaneously applied to prepare polymer brush (PEG)-functionalized MOF materials (UiO-66-NH2) and immobilized with Ti4+ (MOF-Brush-THBA-Ti4+) for phosphopeptide analysis. The material has a detection limit of 0.5 fmol, a selectivity of 2000:1, and a loading capacity of 133 mg/g for phosphopeptides. It also demonstrated great repeatability (10 cycles) and recovery rate (96.7 ± 1.4%). During the analysis of bio-samples, 4 specific phosphopeptides were identified in endogenous breast cancer serum, while 11 phosphopeptides were identified in skimmed milk. Moreover, 47 phosphopeptides correlated with 29 phosphorylated proteins were selectively identified from normal control serum, and 66 phosphopeptides correlated with 26 phosphorylated proteins were identified from breast cancer serum. Further analysis of gene ontology (GO) revealed that the detected phosphorylated proteins associated with breast cancer included positive regulation of receptor-mediated endocytosis, proteolysis, extracellular exosome, heparin binding, and chaperone binding. These findings suggest that these associated pathways might contribute to the etiology of breast cancer. Overall, this application exhibits enormous potential in the identification of phosphorylated peptides within bio-samples.


Assuntos
Estruturas Metalorgânicas , Leite , Fosfopeptídeos , Titânio , Zircônio , Humanos , Fosfopeptídeos/sangue , Fosfopeptídeos/química , Titânio/química , Zircônio/química , Estruturas Metalorgânicas/química , Leite/química , Animais , Polímeros/química , Feminino , Neoplasias da Mama/sangue , Limite de Detecção , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
16.
Eur J Clin Pharmacol ; 80(3): 335-354, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38197944

RESUMO

INTRODUCTION: Recent studies have found that lipid levels in patients with chronic hepatitis B (CHB) may change during antiviral therapy. OBJECTIVE: To assess the effects of first-line nucleot(s)ide analogues (NAs) on lipid profiles in patients with CHB using network meta-analysis. METHODS: Seven electronic databases (PubMed, Embase, Cochrane Library, and four Chinese databases) were searched for cohort studies on the effect of NA on lipids in patients with CHB up to August 1, 2023. The changes of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were taken as outcomes. The mean difference (MD) of continuous variables and 95% confidence intervals (CI) were calculated using RevMan 5.4 and Stata 16.0 software, and network meta-analysis was based on a frequentist framework. RESULTS: A total of 4194 patients were included in the study, including patients with CHB treated with entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), as well as patients not receiving antiviral therapy [patients with inactive CHB who were not receiving antiviral therapy (referred as inactive CHB patients) and non-HBV-infected patients]. TDF reduced TC levels compared to the non-antiviral group (TDF vs. inactive CHB patients: MD = - 17.27, 95% CI (- 30.03, - 4.47); TDF vs. non-HBV-infected individuals: MD = - 17.10, 95% CI (- 20.13, - 14.07)). TC changes in the TAF and ETV groups were not statistically different from the non-antiviral group (TAF vs. inactive CHB patients: MD = - 2.69, 95% CI (- 14.42, 9.04); TAF vs. non-HBV-infected individuals: MD = - 2.52, 95% CI (- 8.47, 3.43); ETV vs. inactive CHB patients: MD = - 4.24, 95% CI (- 17.12, 8.64); ETV vs. non-HBV-infected individuals: MD = - 4.07, 95% CI (- 9.90, 1.75)). The ranking of the effects for lowering TC is as follows: CHB patients treated with nucleotide analogues [with varying efficacy: TDF (SUCRA = 99.9) > ETV (SUCRA = 59.3) > TAF (SUCRA = 43.6)] > inactive CHB patients (SUCRA = 27.3) > non-HBV-infected individuals (SUCRA = 19.9). As for secondary outcomes, among the three antiviral drugs, TDF had the most significant effect on lowering TG, LDL-C, and HDL-C, but none of the three drugs was statistically different from the non-antiviral group. Subgroup analysis showed that the lipid-lowering effect of TDF was more pronounced in the elderly (≥ 50 years). CONCLUSION: TDF was effective in lipid reduction, particularly pronounced in the older population. TAF and ETV had a neutral effect to TC, TG, LDL-C, and HDL-C. Despite a relative increase in lipids observed in patients transitioning from TDF to TAF or ETV, these changes remained within acceptable limits.


Assuntos
Antivirais , Hepatite B Crônica , Humanos , Antivirais/uso terapêutico , LDL-Colesterol , Hepatite B Crônica/tratamento farmacológico , Metanálise em Rede , Tenofovir/uso terapêutico , Resultado do Tratamento
17.
J Sep Sci ; 47(16): e2400310, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39164910

RESUMO

In this work, a composite hydrogel material consisting of chitosan-based composite hydrogel was prepared by a simple and rapid synthetic method and will be named three-dimensional (3D)-IL-COF-1@CS hydrogel. Possessing a stable 3D network structure and outstanding hydrophilicity, the novel hydrogel is capable of capturing glycopeptides. The 3D-IL-COF-1@CS hydrogel showed good sensitivity (0.1 fmol/µL) and selectivity (1:2000). In addition, 19 glycopeptides were captured in standard samples. In the analysis of human serum, 148 glycopeptides assigned to 72 glycoproteins were assayed in the serum of normal individuals, and 245 glycopeptides corresponding to 100 glycoproteins were found in the serum of colorectal cancer (CRC) patients. More importantly, several functional programs based on Gene Ontology analysis supported molecular biological processes that may be relevant to the pathogenesis of CRC, including aging, fibrinogen complex, and arylesterase activity. The low cost, simplicity, rapid synthesis, and good enrichment performance have a great future in glycoproteomics analysis and related diseases.


Assuntos
Neoplasias Colorretais , Glicopeptídeos , Interações Hidrofóbicas e Hidrofílicas , Humanos , Neoplasias Colorretais/sangue , Glicopeptídeos/sangue , Glicopeptídeos/química , Hidrogéis/química , Polímeros/química , Quitosana/química
18.
BMC Nephrol ; 25(1): 118, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38556867

RESUMO

BACKGROUND: Nonmalignant pleural effusion (NMPE) is common and remains a definite health care problem. Pleural effusion was supposed to be a risk factor for acute kidney injury (AKI). Incidence of AKI in NMPE patients and whether there is correlation between the size of effusions and AKI is unknown. OBJECTIVE: To assess the incidence of AKI in NMPE inpatients and its association with effusion size. STUDY DESIGN AND METHOD: We conducted a retrospective cohort study of inpatients admitted to the Chinese PLA General Hospital with pleural effusion from 2018-2021. All patients with pleural effusions confirmed by chest radiography (CT or X-ray) were included, excluding patients with diagnosis of malignancy, chronic dialysis, end-stage renal disease (ESRD), community-acquired AKI, hospital-acquired AKI before chest radiography, and fewer than two serum creatinine tests during hospitalization. Multivariate logistic regression and LASSO logistic regression models were used to identify risk factors associated with AKI. Subgroup analyses and interaction tests for effusion volume were performed adjusted for the variables selected by LASSO. Causal mediation analysis was used to estimate the mediating effect of heart failure, pneumonia, and eGFR < 60 ml/min/1.73m2 on AKI through effusion volume. RESULTS: NMPE was present in 7.8% of internal medicine inpatients. Of the 3047 patients included, 360 (11.8%) developed AKI during hospitalization. After adjustment by covariates selected by LASSO, moderate and large effusions increased the risk of AKI compared with small effusions (moderate: OR 1.47, 95%CI 1.11-1.94 p = 0.006; large: OR 1.86, 95%CI 1.05-3.20 p = 0.028). No significant modification effect was observed among age, gender, diabetes, bilateral effusions, and eGFR. Volume of effusions mediated 6.8% (p = 0.005), 4.0% (p = 0.046) and 4.6% (p < 0.001) of the effect of heart failure, pneumonia and low eGFR on the development of AKI respectively. CONCLUSION: The incidence of AKI is high among NMPE patients. Moderate and large effusion volume is independently associated with AKI compared to small size. The effusion size acts as a mediator in heart failure, pneumonia, and eGFR.


Assuntos
Injúria Renal Aguda , Insuficiência Cardíaca , Derrame Pleural , Pneumonia , Humanos , Estudos Retrospectivos , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/epidemiologia , Pneumonia/epidemiologia , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/complicações , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/complicações
19.
BMC Public Health ; 24(1): 233, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243159

RESUMO

OBJECTIVE: The association between Metabolic Syndrome (MetS), its components, and the risk of osteoarthritis (OA) has been a topic of conflicting evidence in different studies. The aim of this present study is to investigate the association between MetS, its components, and the risk of OA using data from the UK Biobank. METHODS: A prospective cohort study was conducted in the UK Biobank to assess the risk of osteoarthritis (OA) related to MetS. MetS was defined according to the criteria set by the International Diabetes Federation (IDF). Additionally, lifestyle factors, medications, and the inflammatory marker C-reactive protein (CRP) were included in the model. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). The cumulative risk of OA was analyzed using Kaplan-Meier curves and log-rank tests. To explore potential nonlinear associations between MetS components and OA risk, a restricted cubic splines (RCS) model was employed. In addition, the polygenic risk score (PRS) of OA was calculated to characterize individual genetic risk. RESULTS: A total of 45,581 cases of OA were identified among 370,311 participants, with a median follow-up time of 12.48 years. The study found that individuals with MetS had a 15% higher risk of developing OA (HR = 1.15, 95%CI:1.12-1.19). Additionally, central obesity was associated with a 58% increased risk of OA (HR = 1.58, 95%CI:1.5-1.66), while hyperglycemia was linked to a 13% higher risk (HR = 1.13, 95%CI:1.1-1.15). Dyslipidemia, specifically in triglycerides (HR = 1.07, 95%CI:1.05-1.09) and high-density lipoprotein (HR = 1.05, 95%CI:1.02-1.07), was also found to be slightly associated with OA risk. When stratified by PRS, those in the high PRS group had a significantly higher risk of OA compared to those with a low PRS, whereas no interaction was found between MetS and PRS on OA risks. Furthermore, the presence of MetS significantly increased the risk of OA by up to 35% in individuals with elevated CRP levels (HR = 1.35, 95% CI:1.3-1.4). CONCLUSION: MetS and its components have been found to be associated with an increased risk of OA, particularly in individuals with elevated levels of CRP. These findings highlight the significance of managing MetS as a preventive and intervention measure for OA.


Assuntos
Síndrome Metabólica , Osteoartrite , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Estudos Prospectivos , Bancos de Espécimes Biológicos , Biobanco do Reino Unido , Osteoartrite/epidemiologia , Osteoartrite/complicações , Fatores de Risco , Proteína C-Reativa
20.
Parasitol Res ; 123(10): 347, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39387973

RESUMO

Chicken coccidiosis, caused by Eimeria spp., seriously affects the development of the poultry breeding industry. Currently, extensive studies of chicken coccidiosis are mostly focused on acquired immune responses, while information about the innate immune response of chicken coccidiosis is lacking. Toll-like receptor (TLR), the key molecule of the innate immune response, connects innate and adaptive immune responses and induces an immune response against various pathogen infections. Therefore, the quantitative real-time PCR was used to characterize the expression profile of chicken TLRs (chTLRs) and associated cytokines in the cecal tonsil of chickens infected with Eimeria tenella. The results showed that the expression of chTLR1a, chTLR2a, and chTLR5 was significantly upregulated at 3 h post-infection, while chTLR1b, chTLR2b, chTLR3, chTLR7, chTLR15 and chTLR21 was significantly downregulated (p < 0.05). In addition, chTLR1a expression rapidly reached the peaked expression at 3 h post-infection, while chTLR2b and chTLR15 peaked at 168 h post-infection, and chTLR2a expression was highest among chTLRs, peaking at 48 h post-infection (p < 0.05). For cytokines, interleukin (IL)-6 and tumor necrosis factor (TNF)-α peaked at 96 h post-infection, IL-4 and IL-12 peaked at 144 h post-infection, and interferon-γ expression was highest among cytokines at 120 h post-infection. In addition, IL-12 and IL-17 were markedly upregulated at 6 h post-infection (p < 0.05). These results provide insight into innate immune molecules during E. tenella infection in chickens and suggest that innate immune responses may mediate resistance to chicken coccidiosis.


Assuntos
Ceco , Galinhas , Coccidiose , Citocinas , Eimeria tenella , Doenças das Aves Domésticas , Receptores Toll-Like , Animais , Galinhas/parasitologia , Eimeria tenella/imunologia , Citocinas/metabolismo , Citocinas/genética , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Receptores Toll-Like/imunologia , Doenças das Aves Domésticas/parasitologia , Doenças das Aves Domésticas/imunologia , Ceco/parasitologia , Ceco/imunologia , Coccidiose/veterinária , Coccidiose/imunologia , Coccidiose/parasitologia , Imunidade Inata , Perfilação da Expressão Gênica
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