Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 245
Filtrar
1.
Antioxidants (Basel) ; 13(6)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38929080

RESUMO

Unsaturated fatty acids (UFAs) in beef play a vital role in promoting human health. Long-chain fatty acyl-CoA synthase 1 (ACSL1) is a crucial gene for UFA synthesis in bovine adipocytes. To investigate the protein expression profile during UFA synthesis, we performed a proteomic analysis of bovine adipocytes by RNA interference and non-interference with ACSL1 using label-free techniques. A total of 3558 proteins were identified in both the NC and si-treated groups, of which 1428 were differentially expressed proteins (DEPs; fold change ≥ 1.2 or ≤ 0.83 and p-value < 0.05). The enrichment analysis of the DEPs revealed signaling pathways related to UFA synthesis or metabolism, including cAMP, oxytocin, fatty acid degradation, glycerol metabolism, insulin, and the regulation of lipolysis in adipocytes (p-value < 0.05). Furthermore, based on the enrichment analysis of the DEPs, we screened 50 DEPs that potentially influence the synthesis of UFAs and constructed an interaction network. Moreover, by integrating our previously published transcriptome data, this study established a regulatory network involving differentially expressed long non-coding RNAs (DELs), highlighting 21 DEPs and 13 DELs as key genes involved in UFA synthesis. These findings present potential candidate genes for further investigation into the molecular mechanisms underlying UFA synthesis in bovines, thereby offering insights to enhance the quality of beef and contribute to consumer health in future studies.

2.
Int J Mol Sci ; 25(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38892214

RESUMO

Jeryak is the F1 generation of the cross between Gannan yak and Jersey cattle, which has the advantages of fast growth and high adaptability. The growth and development of skeletal muscle is closely linked to meat production and the quality of meat. However, the molecular regulatory mechanisms of muscle growth differences between Gannan yak and Jeryak analyzed from the perspective of chromatin opening have not been reported. In this study, ATAC-seq was used to analyze the difference of chromatin openness in longissimus muscle of Gannan yak and Jeryak. It was found that chromatin accessibility was more enriched in Jeryak compared to Gannan yak, especially in the range of the transcription start site (TSS) ± 2 kb. GO and KEGG enrichment analysis indicate that differential peak-associated genes are involved in the negative regulation of muscle adaptation and the Hippo signaling pathway. Integration analysis of ATAC-seq and RNA-seq revealed overlapping genes were significantly enriched during skeletal muscle cell differentiation and muscle organ morphogenesis. At the same time, we screened FOXO1, ZBED6, CRY2 and CFL2 for possible involvement in skeletal muscle development, constructed a genes and transcription factors network map, and found that some transcription factors (TFs), including YY1, KLF4, KLF5 and Bach1, were involved in skeletal muscle development. Overall, we have gained a comprehensive understanding of the key factors that impact skeletal muscle development in various breeds of cattle, providing new insights for future analysis of the molecular regulatory mechanisms involved in muscle growth and development.


Assuntos
Músculo Esquelético , RNA-Seq , Animais , Bovinos/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Sequenciamento de Cromatina por Imunoprecipitação , Desenvolvimento Muscular/genética , Cromatina/genética , Cromatina/metabolismo , Carne/análise , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
3.
Genomics ; 116(5): 110889, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38901654

RESUMO

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

4.
Pak J Pharm Sci ; 37(2(Special)): 435-442, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38822547

RESUMO

Depression is a common non-motor symptom of Parkinson's disease. Previous studies demonstrated that hydroxysafflor yellow A had properties of improving motor symptoms of Parkinson's disease. The effect of hydroxysafflor yellow A on depression in Parkinson's disease mice is investigated in this study. To induce Parkinson's disease model, male Swiss mice were exposed to rotenone (30 mg/kg) for 6 weeks. The chronic unpredictable mild stress was employed to induce depression from week 3 to week 6. Sucrose preference, tail suspension, and forced swimming tests were conducted. Golgi and Nissl staining of hippocampus were carried out. The levels of dopamine, 5-hydroxytryptamine and the expression of postsynaptic density protein 95, brain-derived neurotrophic factor in hippocampus were assayed. It showed that HSYA improved the depression-like behaviors of Parkinson's disease mice. Hydroxysafflor yellow A attenuated the injury of nerve and elevated contents of dopamine, 5-hydroxytryptamine in hippocampus. Treatment with hydroxysafflor yellow A also augmented the expression of postsynaptic density protein 95 and brain-derived neurotrophic factor. These findings suggest that hydroxysafflor yellow A ameliorates depression-like behavior in Parkinson's disease mice through regulating the contents of postsynaptic density protein 95 and brain-derived neurotrophic factor, therefore protecting neurons and neuronal dendrites of the hippocampus.


Assuntos
Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo , Chalcona , Depressão , Hipocampo , Quinonas , Serotonina , Animais , Quinonas/farmacologia , Quinonas/uso terapêutico , Chalcona/análogos & derivados , Chalcona/farmacologia , Chalcona/uso terapêutico , Masculino , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Comportamento Animal/efeitos dos fármacos , Serotonina/metabolismo , Dopamina/metabolismo , Rotenona/farmacologia , Modelos Animais de Doenças , Proteína 4 Homóloga a Disks-Large/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/psicologia
5.
Food Chem Toxicol ; 190: 114814, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38876379

RESUMO

Lead (Pb) is a common environmental neurotoxicant that causes behavioral impairments in both rodents and humans. Isochlorogenic acid A (ICAA), a phenolic acid found in a variety of natural sources such as tea, fruits, vegetables, coffee, plant-based food products, and various medicinal plants, exerts multiple effects, including protective effects on the lungs, livers, and intestines. The objective of this study was to investigate the potential neuroprotective effects of ICAA against Pb-induced neurotoxicity in ICR mice. The results indicate that ICAA attenuates Pb-induced anxiety-like behaviors. ICAA reduced neuroinflammation, ferroptosis, and oxidative stress caused by Pb. ICAA successfully mitigated the Pb-induced deficits in the cholinergic system in the brain through the reduction of ACH levels and the enhancement of AChE and BChE activities. ICAA significantly reduced the levels of ferrous iron and MDA in the brain and prevented decreases in GSH, SOD, and GPx activity. Immunofluorescence analysis demonstrated that ICAA attenuated ferroptosis and upregulated GPx4 expression in the context of Pb-induced nerve damage. Additionally, ICAA downregulated TNF-α and IL-6 expression while concurrently enhancing the activations of Nrf2, HO-1, NQO1, BDNF, and CREB in the brains of mice. The inhibition of BDNF, Nrf2 and GPx4 reversed the protective effects of ICAA on Pb-induced ferroptosis in nerve cells. In general, ICAA ameliorates Pb-induced neuroinflammation, ferroptosis, oxidative stress, and anxiety-like behaviors through the activation of the BDNF/Nrf2/GPx4 pathways.

6.
ACS Appl Mater Interfaces ; 16(22): 28134-28146, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38768602

RESUMO

Vessel transplantation is currently considered the "gold standard" treatment for cardiovascular disease. However, ideal artificial vascular grafts should possess good biocompatibility and mechanical strength that match those of native autologous vascular tissue to promote in vivo tissue regeneration. In this study, a series of dynamic cross-linking double-network hydrogels and the resultant hydrogel tubes were prepared. The hydrogels (named PCO), composed of rigid poly(vinyl alcohol) (PVA), flexible carboxymethyl chitosan (CMCS), and a cross-linker of aldehyde-based ß-cyclodextrin (OCD), were formed in a double-network structure with multiple dynamical cross-linking including dynamic imine bonds, hydrogen bonds, and microcrystalline regions. The PCO hydrogels exhibited superior mechanical strength, good network stability, and fatigue resistance. Additionally, it demonstrated excellent cell and blood compatibility. The results showed that the introduction of CMCS/OCD led to a significant increase in the proliferation rate of endothelial cells seeded on the surface of the hydrogel. The hemolysis rate in the test was lower than 0.3%, and both protein adsorption and platelet adhesion were reduced, indicating an excellent anticoagulant function. The plasma recalcification time test results showed that endogenous coagulation was alleviated to some extent. When formed into blood vessels and incubated with blood, no thrombus formation was observed, and there was minimal red blood cell aggregation. Therefore, this novel hydrogel tube, with excellent mechanical properties, exhibits antiadhesive characteristics toward blood cells and proteins, as well as antithrombotic properties, making it hold tremendous potential for applications in the biomedical and engineering fields.


Assuntos
Materiais Biocompatíveis , Quitosana , Hidrogéis , Álcool de Polivinil , Hidrogéis/química , Hidrogéis/farmacologia , Hidrogéis/síntese química , Quitosana/química , Quitosana/análogos & derivados , Quitosana/farmacologia , Humanos , Álcool de Polivinil/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Prótese Vascular , Teste de Materiais , beta-Ciclodextrinas/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Animais , Adesividade Plaquetária/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química
7.
Toxicol Res (Camb) ; 13(3): tfae072, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38737339

RESUMO

Lead (Pb) is a nonessential heavy metal, which can cause many health problems. Isochlorogenic acid A (ICAA), a phenolic acid present in tea, fruits, vegetables, coffee, plant-based food products, and various medicinal plants, exerts multiple effects, including anti-oxidant, antiviral, anti-inflammatory and antifibrotic functions. Thus, the purpose of our study was to determine if ICAA could prevent Pb-induced hepatotoxicity in ICR mice. An evaluation was performed on oxidative stress, inflammation and fibrosis, and related signaling. The results indicate that ICAA attenuates Pb-induced abnormal liver function. ICAA reduced liver fibrosis, inflammation and oxidative stress caused by Pb. ICAA abated Pb-induced fibrosis and decreased inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α). ICAA abrogated reductions in activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Masson staining revealed that ICAA reduced collagen fiber deposition in Pb-induced fibrotic livers. Western blot and immunohistochemistry analyses showed ICAA increased phosphorylated AMP-activated protein kinase (p-AMPK) expression. ICAA also reduced the expression of collagen I, α-smooth muscle actin (α-SMA), phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated c-jun N-terminal kinase (p-JNK), p-p38, phosphorylated signal transducer and phosphorylated activator of transcription 3 (p-STAT3), transforming growth factor ß1 (TGF-ß1), and p-Smad2/3 in livers of mice. Overall, ICAA ameliorates Pb-induced hepatitis and fibrosis by inhibiting the AMPK/MAPKs/NF-κB and STAT3/TGF-ß1/Smad2/3 pathways.

8.
ChemSusChem ; : e202400827, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38785150

RESUMO

Ozonation water treatment technology has attracted increasing attention due to its environmental benign and high efficiency. Rutile PbO2 is a promising anode material for electrochemical ozone production (EOP). However, the reaction mechanism underlying ozone production catalyzed by PbO2 was rarely studied and not well-understood, which was in part due to the overlook of the electrochemistry-driven formation of oxygen vacancy (OV) of PbO2. Herein, we unrevealed the origin of the EOP activity of PbO2 starting from the electrochemical surface state analysis using density functional theory (DFT) calculations, activity analysis, and catalytic volcano modeling. Interestingly, we found that under experimental EOP potential (i.e., a potential around 2.2 V vs. reversible hydrogen electrode), OV can still be generated easily on PbO2 surfaces. Our subsequent kinetic and thermodynamic analyses show that these OV sites on PbO2 surfaces are highly active for the EOP reaction through an interesting atomic oxygen (O*)-O2 coupled mechanism. In particular, rutile PbO2(101) with the "in-situ" generated OV exhibited superior EOP activities, outperforming (111) and (110). Finally, by catalytic modeling, we found that PbO2 is close to the theoretical optimum of the reaction, suggesting a superior EOP performance of rutile PbO2. All these analyses are in good agreement with experimental observations.

9.
Nat Plants ; 10(5): 771-784, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38684916

RESUMO

The fall armyworm (FAW) poses a significant threat to global crop production. Here we showed that overexpression of jasmonate ZIM-domain (JAZ) protein GhJAZ24 confers resistance to cotton bollworm and FAW, while also causing sterility in transgenic cotton by recruiting TOPLESS and histone deacetylase 6. We identified the NGR motif of GhJAZ24 that recognizes and binds the aminopeptidase N receptor, enabling GhJAZ24 to enter cells and disrupt histone deacetylase 3, leading to cell death. To overcome plant sterility associated with GhJAZ24 overexpression, we developed iJAZ (i, induced), an approach involving damage-induced expression and a switch from intracellular to extracellular localization of GhJAZ24. iJAZ transgenic cotton maintained fertility and showed insecticidal activity against cotton bollworm and FAW. In addition, iJAZ transgenic rice, maize and tobacco plants showed insecticidal activity against their lepidopteran pests, resulting in an iJAZ-based approach for generating alternative insecticidal proteins with distinctive mechanisms of action, thus holding immense potential for future crop engineering.


Assuntos
Produtos Agrícolas , Gossypium , Mariposas , Plantas Geneticamente Modificadas , Animais , Produtos Agrícolas/genética , Mariposas/fisiologia , Mariposas/genética , Gossypium/genética , Gossypium/parasitologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oryza/genética , Oryza/parasitologia , Zea mays/genética , Zea mays/parasitologia , Nicotiana/genética , Nicotiana/parasitologia
10.
Brain Sci ; 14(4)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38671952

RESUMO

Parkinson's disease (PD) is characterized not only by motor symptoms but also by non-motor dysfunctions, such as olfactory impairment; the cause is not fully understood. Our study suggests that neuronal loss and inflammation in brain regions along the olfactory pathway, such as the olfactory bulb (OB) and the piriform cortex (PC), may contribute to olfactory dysfunction in PD mice, which might be related to the downregulation of the trace amine-associated receptor 1 (TAAR1) in these areas. In the striatum, although only a decrease in mRNA level, but not in protein level, of TAAR1 was detected, bioinformatic analyses substantiated its correlation with PD. Moreover, we discovered that neuronal death and inflammation in the OB and the PC in PD mice might be regulated by TAAR through the Bcl-2/caspase3 pathway. This manifested as a decrease of anti-apoptotic protein Bcl-2 and an increase of the pro-apoptotic protein cleaved caspase3, or through regulating astrocytes activity, manifested as the increase of TAAR1 in astrocytes, which might lead to the decreased clearance of glutamate and consequent neurotoxicity. In summary, we have identified a possible mechanism to elucidate the olfactory dysfunction in PD, positing neuronal damage and inflammation due to apoptosis and astrocyte activity along the olfactory pathway in conjunction with the downregulation of TAAR1.

11.
Colorectal Dis ; 26(5): 886-898, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38594838

RESUMO

AIM: Restorative proctocolectomy with transabdominal ileal pouch-anal anastomosis (abd-IPAA) has become the standard surgical treatment for medically refractory ulcerative colitis (UC). However, it requires a technically difficult distal anorectal dissection and anastomosis due to the bony confines of the deep pelvis. To address these challenges, the transanal IPAA approach (ta-IPAA) was developed. This novel approach may offer increased visibility and range of motion compared with abd-IPAA, although its postoperative benefits remain unclear. The aim of this work was to perform a systematic review and meta-analysis to compare and inform the frequency of postoperative outcomes between ta-IPAA and abd-IPAA for patients with UC. METHOD: Several databases were searched from inception until May 2022 for studies reporting postoperative outcomes of patients undergoing ta-IPAA. Reviewers, working independently and in duplicate, evaluated studies for inclusion and graded the risk of bias. Odds ratios (OR), mean differences (MD) and prevalence ratio (PR) and their corresponding 95% confidence intervals (CIs) were calculated using random-effects models. Sensitivity analysis was performed. RESULTS: Ten retrospective studies comprising 284 patients with ta-IPAA were included. Total mesorectal excision was performed in 61.8% of cases and close rectal dissection in 27.9%. There was no difference in the odds of Clavien-Dindo (CD) I-II complications, CD III-IV and anastomotic leak (OR 0.96, 95% CI 0.27-3.40; OR 1.18, 95% CI 0.65-2.16; OR 1.37, 95% CI 0.58-3.23; respectively) between ta-IPAA and abd-IPAA. The ta-IPAA pooled CD I-II complication rate was 18% (95% CI 5%-35%) and for CD III-IV 10% (95% CI 5%-17%), and the anastomotic leak rate was 6% (95% CI 2%-10%). There were no deaths reported. CONCLUSIONS: This meta-analysis compared the novel ta-IPAA procedure with abd-IPAA and found no difference in postoperative outcomes. While the need for randomized controlled trails and comparison of functional outcomes between both approaches remains, this evidence should assist colorectal surgeons to decide if ta-IPAA is a viable alternative.


Assuntos
Colite Ulcerativa , Complicações Pós-Operatórias , Proctocolectomia Restauradora , Humanos , Proctocolectomia Restauradora/métodos , Proctocolectomia Restauradora/efeitos adversos , Colite Ulcerativa/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Bolsas Cólicas/efeitos adversos , Canal Anal/cirurgia , Feminino , Masculino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Anastomose Cirúrgica/métodos , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologia , Cirurgia Endoscópica Transanal/métodos , Cirurgia Endoscópica Transanal/efeitos adversos , Doenças Inflamatórias Intestinais/cirurgia
12.
J Agric Food Chem ; 72(18): 10428-10438, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38660720

RESUMO

Tebuconazole is a chiral triazole fungicide used globally in agriculture as a racemic mixture, but its enantiomers exhibit significant enantioselective dissimilarities in bioactivity and environmental behaviors. The steric hindrance caused by the tert-butyl group makes it a great challenge to synthesize tebuconazole enantiomers. Here, we designed a simple chemoenzymatic approach for the asymmetric synthesis of (R)-tebuconazole, which includes the biocatalytic resolution of racemic epoxy-precursor (2-tert-butyl-2-[2-(4-chlorophenyl)ethyl] oxirane, rac-1a) by Escherichia coli/Rpeh whole cells expressed epoxide hydrolase from Rhodotorula paludigensis (RpEH), followed by a one-step chemocatalytic synthesis of (R)-tebuconazole. It was observed that (S)-1a was preferentially hydrolyzed by E. coli/Rpeh, whereas (R)-1a was retained with a specific activity of 103.8 U/g wet cells and a moderate enantiomeric ratio (E value) of 13.4, which was remarkably improved to 43.8 after optimizing the reaction conditions. Additionally, a gram-scale resolution of 200 mM rac-1a was performed using 150 mg/mL E. coli/Rpeh wet cells, resulting in the retention of (R)-1a in a 97.0% ees, a 42.5% yields, and a 40.5 g/L/d space-time yield. Subsequently, the synthesis of highly optical purity (R)-tebuconazole (>99% ee) was easily achieved through the chemocatalytic ring-opening of the epoxy-precursor (R)-1a with 1,2,4-triazole. To elucidate insight into the enantioselectivity, molecular docking simulations revealed that the unique L-shaped substrate-binding pocket of RpEH plays a crucial role in the enantioselective recognition of bulky 2,2-disubstituted oxirane 1a.


Assuntos
Biocatálise , Epóxido Hidrolases , Proteínas Fúngicas , Fungicidas Industriais , Rhodotorula , Triazóis , Rhodotorula/enzimologia , Rhodotorula/química , Rhodotorula/metabolismo , Triazóis/química , Triazóis/metabolismo , Fungicidas Industriais/química , Fungicidas Industriais/metabolismo , Fungicidas Industriais/síntese química , Epóxido Hidrolases/metabolismo , Epóxido Hidrolases/química , Estereoisomerismo , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Simulação de Acoplamento Molecular , Escherichia coli/enzimologia , Escherichia coli/metabolismo
13.
Lancet Infect Dis ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38614117

RESUMO

BACKGROUND: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine). METHODS: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China. Healthy children aged 3-12 years with no history of varicella infection or vaccination were enrolled and randomly assigned (1:1:1:1) to receive a single subcutaneous injection of the v7D vaccine at 3·3 log10 plaque forming units (PFU; low-dose v7D group), 3·9 log10 PFU (medium-dose v7D group), and 4·2 log10 PFU (high-dose v7D group), or the positive control varicella vaccine (vOka vaccine group). All the participants, laboratory personnel, and investigators other than the vaccine preparation and management staff were masked to the vaccine allocation. The primary outcome was assessment of the geometric mean titres (GMTs) and seroconversion rates of anti-varicella zoster virus immunoglobulin G (IgG) induced by different dose groups of v7D vaccine at 0, 42, 60, and 90 days after vaccination in the per-protocol set for humoral immune response analysis. Safety was a secondary outcome, focusing on adverse events within 42 days post-vaccination, and serious adverse events within 6 months after vaccination. This study was registered on Chinese Clinical Trial Registry, ChiCTR2000034434. FINDINGS: On Aug 18-21, 2020, 842 eligible volunteers were enrolled and randomly assigned treatment. After three participants withdrew, 839 received a low dose (n=211), middle dose (n=210), or high dose (n=210) of v7D vaccine, or the vOka vaccine (n=208). In the per-protocol set for humoral immune response analysis, the anti-varicella zoster virus IgG antibody response was highest at day 90. At day 90, the seroconversion rates of the low-dose, medium-dose, and high-dose groups of v7D vaccine and the positive control vOka vaccine group were 100·0% (95% CI 95·8-100·0; 87 of 87 participants), 98·9% (93·8-100·0; 87 of 88 participants), 97·8% (92·4-99·7; 91 of 93 participants), and 96·4% (89·8-99·2; 80 of 83 participants), respectively; the GMTs corresponded to values of 30·8 (95% CI 26·2-36·0), 31·3 (26·7-36·6), 28·2 (23·9-33·2), and 38·5 (31·7-46·7). The v7D vaccine, at low dose and medium dose, elicited a humoral immune response similar to that of the vOka vaccine. However, the high-dose v7D vaccine induced a marginally lower GMT compared with the vOka vaccine at day 90 (p=0·027). In the per-protocol set, the three dose groups of the v7D vaccine induced a similar humoral immune response at each timepoint, with no statistically significant differences. The incidence of adverse reactions in the low-dose, medium-dose, and high-dose groups of v7D vaccine was significantly lower than that in the vOka vaccine group (17% [35 of 211 participants], 20% [41 of 210 participants], and 13% [27 of 210 participants] vs 24% [50 of 208 participants], respectively; p=0·025), especially local adverse reactions (10% [22 of 211 participants], 14% [30 of 210 participants] and 9% [18 of 210 participants] vs 18% [38 of 208 participants], respectively; p=0·016). None of the serious adverse events were vaccine related. INTERPRETATION: The three dose groups of the candidate v7D vaccine exhibit similar humoral immunogenicity to the vOka vaccine and are well tolerated. These findings encourage further investigations on two-dose vaccination schedules, efficacy, and the potential safety benefit of v7D vaccine in the future. FUNDING: The National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, the Fundamental Research Funds for the Central Universities, and Beijing Wantai. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

14.
Epigenetics ; 19(1): 2337087, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38564758

RESUMO

Decidual macrophages are the second-largest immune cell group at the maternal-foetal interface. They participate in apoptotic cell removal, and protect the foetus from microorganisms or pathogens. Dysfunction of decidual macrophages gives rise to pregnancy complications such as preeclampsia and recurrent spontaneous miscarriage (RSM). However, the mechanisms by which decidual macrophages are involved in the occurrence of adverse pregnancy outcomes have not been elucidated. Here we integrated DNA methylation and gene expression data from decidua macrophages to identify potential risk factors related to RSM. GPR133 was significantly hypomethylated and upregulated in decidual macrophages from RSM patients. Further demethylation analysis demonstrated that GPR133 expression in decidual macrophages was significantly increased by 5-Aza-dC treatment. In addition, the influence of GPR133 on the phagocytic ability of macrophages was explored. Phagocytosis was impaired in the decidual macrophages of RSM patients with increased GPR133 expression. Increased GPR133 expression induced by demethylation treatment in the decidual macrophages of healthy control patients led to a significant decrease in phagocytic function. Importantly, knockdown of GPR133 resulted in a significant improvement in the phagocytic function of THP-1 macrophages. In conclusion, the existing studies have shown the influence of GPR133 on the phagocytic function of decidual macrophages and pregnancy outcomes, providing new data and ideas for future research on the role of decidual macrophages in RSM.


Assuntos
Aborto Espontâneo , Decídua , Feminino , Humanos , Gravidez , Aborto Espontâneo/genética , Decídua/metabolismo , Metilação de DNA , Macrófagos , Fagocitose , Regulação para Cima
15.
Dis Colon Rectum ; 67(7): 929-939, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38517090

RESUMO

BACKGROUND: A complete total mesorectal excision is the criterion standard in curative rectal cancer surgery. Ensuring quality is challenging in a narrow pelvis, and obesity amplifies technical difficulties. Pelvimetry is the measurement of pelvic dimensions, but its role in gauging preoperatively the difficulty of proctectomy is largely unexplored. OBJECTIVE: To determine pelvic structural factors associated with incomplete total mesorectal excision after curative proctectomy and build a predictive model for total mesorectal excision quality. DESIGN: Retrospective cohort study. SETTING: A quaternary referral center database of patients diagnosed with rectal adenocarcinoma (2009-2017). PATIENTS: Curative-intent proctectomy for rectal adenocarcinoma. INTERVENTIONS: All radiological measurements were obtained from preoperative CT images using validated imaging processing software tools. Completeness of total mesorectal excision was obtained from histology reports. MAIN OUTCOME MEASURES: Ability of radiological pelvimetry and obesity measurements to predict total mesorectal excision quality. RESULTS: Of the 410 cases meeting inclusion criteria, 362 underwent a complete total mesorectal excision (88%). Multivariable regression identified a deeper sacral curve (per 100 mm 2 [OR: 1.14; 95% CI, 1.06-1.23; p < 0.001]) and a greater transverse distance of the pelvic outlet (per 10 mm [OR:1.41, 95% CI, 1.08-1.84; p = 0.012]) to be independently associated with incomplete total mesorectal excision. An increased area of the pelvic inlet (per 10 cm 2 [OR: 0.85; 95% CI, 0.75-0.97; p = 0.02) was associated with a higher rate of complete mesorectal excision. No difference in visceral obesity ratio and visceral obesity (ratio >0.4 vs <0.4) between BMI (<30 vs ≥30) and sex was identified. A model was built to predict mesorectal quality using the following variables: depth of sacral curve, area of pelvic inlet, and transverse distance of the pelvic outlet. LIMITATIONS: Retrospective analysis is not controlled for the choice of surgical approach. CONCLUSIONS: Pelvimetry predicts total mesorectal excision quality in rectal cancer surgery and can alert surgeons preoperatively to cases of unusual difficulty. This predictive model may contribute to treatment strategy and aid in the comparison of outcomes between traditional and novel techniques of total mesorectal excision. See Video Abstract . USO DE MEDICIONES DE PELVIMETRA Y OBESIDAD VISCERAL BASADAS EN TC PARA PREDECIR LA CALIDAD DE TME EN PACIENTES SOMETIDOS A CIRUGA DE CNCER DE RECTO: ANTECEDENTES:Una escisión mesorrectal total y completa es el estándar de oro en la cirugía curativa del cáncer de recto. Garantizar la calidad es un desafío en una pelvis estrecha y la obesidad amplifica las dificultades técnicas. La pelvimetría es la medición de las dimensiones pélvicas, pero su papel para medir la dificultad preoperatoria de la proctectomía está en gran medida inexplorado.OBJETIVO:Determinar los factores estructurales pélvicos asociados con la escisión mesorrectal total incompleta después de una proctectomía curativa y construir un modelo predictivo para la calidad de la escisión mesorrectal total.DISEÑO:Estudio de cohorte retrospectivo.ÁMBITO:Base de datos de un centro de referencia cuaternario de pacientes diagnosticados con adenocarcinoma de recto (2009-2017).PACIENTES:Proctectomía con intención curativa para adenocarcinoma de recto.INTERVENCIONES:Todas las mediciones radiológicas se obtuvieron a partir de imágenes de TC preoperatorias utilizando herramientas de software de procesamiento de imágenes validadas. La integridad de la escisión mesorrectal total se obtuvo a partir de informes histológicos.PRINCIPALES MEDIDAS DE VALORACIÓN:Capacidad de la pelvimetría radiológica y las mediciones de obesidad para predecir la calidad total de la escisión mesorrectal.RESULTADOS:De los 410 casos que cumplieron los criterios de inclusión, 362 tuvieron una escisión mesorrectal total completa (88%). Una regresión multivariable identificó una curva sacra más profunda (por 100 mm2); OR:1,14,[IC95%:1,06-1,23,p<0,001], y mayor distancia transversal de salida pélvica (por 10mm); OR:1,41, [IC 95%:1,08-1,84,p=0,012] como asociación independiente con escisión mesorrectal total incompleta. Un área aumentada de entrada pélvica (por 10 cm2); OR:0,85, [IC95%:0,75-0,97,p=0,02] se asoció con una mayor tasa de escisión mesorrectal completa. No se identificaron diferencias en la proporción de obesidad visceral y la obesidad visceral (proporción>0,4 vs.<0,4) entre el índice de masa corporal (<30 vs.>=30) o el sexo. Se construyó un modelo para predecir la calidad mesorrectal utilizando variables: profundidad de la curva sacra, área de la entrada pélvica y distancia transversal de la salida pélvica.LIMITACIONES:Análisis retrospectivo no controlado por la elección del abordaje quirúrgico.CONCLUSIONES:La pelvimetría predice la calidad de la escisión mesorrectal total en la cirugía del cáncer de recto y puede alertar a los cirujanos preoperatoriamente sobre casos de dificultad inusual. Este modelo predictivo puede contribuir a la estrategia de tratamiento y ayudar en la comparación de resultados entre técnicas tradicionales y novedosas de escisión mesorrectal total. (Traducción- Dr. Ingrid Melo).


Assuntos
Adenocarcinoma , Obesidade Abdominal , Pelvimetria , Protectomia , Neoplasias Retais , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/patologia , Masculino , Feminino , Estudos Retrospectivos , Protectomia/métodos , Pessoa de Meia-Idade , Idoso , Pelvimetria/métodos , Adenocarcinoma/cirurgia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Tomografia Computadorizada por Raios X/métodos , Obesidade Abdominal/diagnóstico por imagem , Pelve/diagnóstico por imagem , Reto/cirurgia , Reto/diagnóstico por imagem
16.
Int J Biol Macromol ; 265(Pt 1): 130447, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458280

RESUMO

The increased use and expansion of biomass applications offer a viable approach to diminish reliance on petroleum-derived resources and promote carbon neutrality. Cellulose, being the most abundant natural polymer on Earth, has garnered considerable attention. This study introduces a straightforward method to fabricate a cellulose-based multifunctional composite film designed for efficient light management, specifically featuring flame retardant and thermal-healing capabilities. The film incorporates a microfibrillated cellulose (MFC) matrix with functional components, namely benzoxazine resin (BR) and 2-hydroxyethyl methacrylate phosphate (HEMAP). Utilizing dynamic covalent crosslinking, the composite films exhibit satisfactory self-healing properties. The combined effects of BR and HEMAP contribute to the effective flame retardancy of the composite film. Furthermore, the resulting film shields ultraviolet and blue light, offering comfortable interior lighting by mitigating harsh light and extending light propagation. The film also demonstrates favorable water resistance and high tensile strength. The exceptional multifunctional properties, coupled with its safety and extended service life, position it as a potential optical management film for smart building materials.


Assuntos
Celulose , Retardadores de Chama , Polímeros , Benzoxazinas , Biomassa
17.
Int J Mol Sci ; 25(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38473754

RESUMO

Muscle formation directly determines meat production and quality. The non-SMC condensin I complex subunit G (NCAPG) is strongly linked to the growth features of domestic animals because it is essential in controlling muscle growth and development. This study aims to elucidate the tissue expression level of the bovine NCAPG gene, and determine the key transcription factors for regulating the bovine NCAPG gene. In this study, we observed that the bovine NCAPG gene exhibited high expression levels in longissimus dorsi and spleen tissues. Subsequently, we cloned and characterized the promoter region of the bovine NCAPG gene, consisting of a 2039 bp sequence, through constructing the deletion fragment double-luciferase reporter vector and site-directed mutation-identifying core promoter region with its key transcription factor binding site. In addition, the key transcription factors of the core promoter sequence of the bovine NCAPG gene were analyzed and predicted using online software. Furthermore, by integrating overexpression experiments and the electrophoretic mobility shift assay (EMSA), we have shown that cAMP response element binding protein 1 (CREB1) and myogenic differentiation 1 (MYOD1) bind to the core promoter region (-598/+87), activating transcription activity in the bovine NCAPG gene. In conclusion, these findings shed important light on the regulatory network mechanism that underlies the expression of the NCAPG gene throughout the development of the muscles in beef cattle.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Regulação da Expressão Gênica , Bovinos , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Regiões Promotoras Genéticas , Mioblastos
18.
Plant Cell ; 36(5): 2000-2020, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38299379

RESUMO

The flower-infecting fungus Ustilaginoidea virens causes rice false smut, which is a severe emerging disease threatening rice (Oryza sativa) production worldwide. False smut not only reduces yield, but more importantly produces toxins on grains, posing a great threat to food safety. U. virens invades spikelets via the gap between the 2 bracts (lemma and palea) enclosing the floret and specifically infects the stamen and pistil. Molecular mechanisms for the U. virens-rice interaction are largely unknown. Here, we demonstrate that rice flowers predominantly employ chitin-triggered immunity against U. virens in the lemma and palea, rather than in the stamen and pistil. We identify a crucial U. virens virulence factor, named UvGH18.1, which carries glycoside hydrolase activity. Mechanistically, UvGH18.1 functions by binding to and hydrolyzing immune elicitor chitin and interacting with the chitin receptor CHITIN ELICITOR BINDING PROTEIN (OsCEBiP) and co-receptor CHITIN ELICITOR RECEPTOR KINASE1 (OsCERK1) to impair their chitin-induced dimerization, suppressing host immunity exerted at the lemma and palea for gaining access to the stamen and pistil. Conversely, pretreatment on spikelets with chitin induces a defense response in the lemma and palea, promoting resistance against U. virens. Collectively, our data uncover a mechanism for a U. virens virulence factor and the critical location of the host-pathogen interaction in flowers and provide a potential strategy to control rice false smut disease.


Assuntos
Quitina , Flores , Hypocreales , Oryza , Doenças das Plantas , Oryza/microbiologia , Oryza/metabolismo , Oryza/genética , Doenças das Plantas/microbiologia , Quitina/metabolismo , Flores/microbiologia , Hypocreales/patogenicidade , Hypocreales/genética , Hypocreales/metabolismo , Transdução de Sinais , Interações Hospedeiro-Patógeno , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Virulência , Fatores de Virulência/metabolismo , Fatores de Virulência/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética
19.
Arch Virol ; 169(3): 42, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332318

RESUMO

Beauveria bassiana Vuillemin is an entomopathogenic fungus that has been developed as a biological insecticide. B. bassiana can be infected by single or multiple mycoviruses, most of which are double-stranded RNA (dsRNA) viruses, while infections with single-stranded RNA (ssRNA) viruses, especially negative single-stranded RNA (-ssRNA) viruses, have been observed less frequently. In the present study, we sequenced and analyzed the complete genomes of two new different mycoviruses coinfecting a single B. bassiana strain: a -ssRNA virus which we have named "Beauveria bassiana negative-strand RNA virus 1" (BbNSRV1), and a dsRNA virus, which we have named "Beauveria bassiana orthocurvulavirus 1" (BbOCuV1). The genome of BbNSRV1 consists of a single segment of negative-sense, single-stranded RNA with a length of 6169 nt, containing a single open reading frame (ORF) encoding a putative RNA-dependent RNA polymerase (RdRp) with 1949 aa (220.1 kDa). BLASTx analysis showed that the RdRp had the highest sequence similarity (59.79%) to that of Plasmopara viticola lesion associated mononegaambi virus 2, a member of the family Mymonaviridae. This is the first report of a -ssRNA mycovirus infecting B. bassiana. The genome of BbOCuV1 consists of two dsRNA segments, 2164 bp and 1765 bp in length, respectively, with dsRNA1 encoding a protein with conserved RdRp motifs and 70.75% sequence identity to the putative RdRp of the taxonomically unassigned mycovirus Fusarium graminearum virus 5 (FgV5), and the dsRNA2 encoding a putative coat protein with sequence identity 64.26% to the corresponding protein of the FgV5. Phylogenetic analysis indicated that BbOCuV1 belongs to a taxonomically unassigned group of dsRNA mycoviruses related to members of the families Curvulaviridae and Partitiviridae. Hence, it might be the member of a new family that remains to be named and formally recognized.


Assuntos
Beauveria , Micovírus , Vírus de RNA , Vírus , Humanos , Beauveria/genética , RNA de Cadeia Dupla/genética , Filogenia , Genoma Viral , Vírus de RNA/genética , Vírus/genética , Vírus de RNA de Cadeia Dupla/genética , Micovírus/genética , RNA Polimerase Dependente de RNA/genética , RNA Viral/genética , Fases de Leitura Aberta
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...