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1.
Br Poult Sci ; : 1-11, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39364777

RESUMO

1. In the following experiment meat quality traits of a Gushi-Anka F2 resource population were measured, and their heritability estimated. Intramuscular fat (IMF) had medium heritability (0.35) but leg muscle fibre density (LMD), leg muscle fibre diameter (LMF), breast muscle fibre density (BMD), fresh fat content (FFA), and absolute dry fat content (AFC) had low heritability (0-0.2). The IMF presented the most important genetic additive effect among the poultry meat quality-related traits studied.2. The phenotypic data of meat quality traits in the Gushi-Anka F2 resource population were combined with genotyping by sequencing (GBS) data to obtain genotype data. Six meat quality traits in 734 birds were analysed by GWAS. Based on these variants, 83 significant (-log10(p) > 4.42) single nucleotide polymorphisms and four quantitative trait loci (QTL) regions corresponding to 175 genes were identified. Further linkage disequilibrium (LD) analysis was conducted on chromosome 13 (Chr13) and chromosome 27 (Chr27) QTL regions.3. Based on the transcriptome data and GWAS results, 12 shared genes - ITGB3, DNAJC27, ETV4, C7orf50, FKBP1B, G3BP1, IGF2BP1, KCNH6, LOC416263, SCARA5, SMIM5 and TBL1XR1 were identified as candidate genes influencing muscle fibre and fat traits.

4.
Eur Rev Med Pharmacol Sci ; 28(18): 4276, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39359204

RESUMO

The article "Effects of fibroblast growth factors 2 and low intensity pulsed ultrasound on the repair of knee articular cartilage in rabbits" by Z.-F. Tang, H.-Y. Li, published in Eur Rev Med Pharmacol Sci 2018; 22 (8): 2447-2453 - PMID: 29762847 has been retracted by the Editor in Chief. Following some concerns raised on PubPeer (link: https://pubpeer.com/publications/F11DC0DC2B3DAB9753C11C8DC18822), the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure manipulation. The authors have been informed about the journal's investigation but remained unresponsive and have not provided the study's raw data. The journal's investigation identified duplications between Control images A (4 weeks) and E (8 weeks), FHF2 C (4 weeks) and G (8 weeks), and FGF2+LIPU D (4 weeks)  and H (8 weeks) of Figure 1. Additionally, duplications were identified between panels A and B of Figure 4. Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. This article has been retracted. The Publisher apologizes for any inconvenience this may cause.

5.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(8): 1485-1496, 2024 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-39276044

RESUMO

OBJECTIVE: To explore the targets and pathways of Cynanchum wilfordii for treatment of ulcerative colitis (UC). METHODS: UPLC-QE-MS was used to identify the components of Cynanchum wilfordii ethanol extract, and their targets were screened using public databases for construction of the core protein-protein interaction (PPI) network and GO and KEGG enrichment analyses. Forty male C57 mice were randomized into normal control group, model group, mesalazine group and Cynanchum wilfordii group (n=10), and in the latter 3 groups, mouse UC models were established by treatment with 2.5% DSS and the latter 2 groups drug interventions by gavage. The therapeutic effect was evaluated by recording body weight changes and DAI score. Pathological changes of the colon tissue were observed with HE and AB-PAS staining, and JAK2 and STAT3 protein expressions were detected with Western blotting. The metabolites and metabolic pathways were identified by metabonomics analysis. RESULTS: We identified 240 chemical components in Cynanchum wilfordii alcoholic extracts, including 19 steroids. A total of 177 Cynanchum wilfordii targets, 5406 UC genes, and 117 intersection genes were obtained. JAK2 and STAT3 were the core targets and significantly enriched in lipid and atherosclerosis pathways. Cynanchum wilfordii treatment significantly increased the body weight and decreased DAI score of UC mice (P < 0.05), alleviated intestinal pathologies, and decreased JAK2 and STAT3 protein expressions in the colon tissues. Most of the 83 intersecting differential metabolites between the control, model and Cynanchum wilfordii groups were identified as glycerophospholipids, arachidonic acid, and amino acids involving glycerophospholipid metabolism and other pathways. Correlation analysis suggested that the core targets of Cynanchum wilfordii for UC participated in regulation of the metabolites. CONCLUSION: Cynanchum wilfordii alleviates lipid and amino acid metabolism disorders to lessen UC in mice by regulating the core targets including JAK2 and STAT3 and the levels of endogenous metabolites.


Assuntos
Colite Ulcerativa , Cynanchum , Metabolômica , Camundongos Endogâmicos C57BL , Farmacologia em Rede , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Camundongos , Masculino , Cynanchum/química , Fator de Transcrição STAT3/metabolismo , Modelos Animais de Doenças , Extratos Vegetais/farmacologia , Janus Quinase 2/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Cromatografia Líquida de Alta Pressão , Mapas de Interação de Proteínas
6.
Antimicrob Agents Chemother ; 68(10): e0067024, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39254297

RESUMO

Ceftazidime-avibactam (CZA) and ceftolozane-tazobactam (C/T) are important agents for treating multidrug-resistant P. aeruginosa infections. In this study, we evaluated the molecular characteristics of 300 globally collected clinical P. aeruginosa isolates non-susceptible (NS) to CZA, C/T, or both agents. Isolates were CZA-NS and C/T-NS (n = 57), CZA-susceptible (S) and C/T-NS (n = 145), or CZA-NS and C/T-S (n = 98) selected from the Antimicrobial Testing Leadership and Surveillance (ATLAS) surveillance program from 2020 to 2021. Characterization was by whole-genome sequencing. Analysis was performed to identify ß-lactamase genes and mutations that impact efflux regulation, AmpC regulation, and target binding (PBP3). Of the 57 CZA-NS+C/T-NS isolates, 64.9% carried a metallo-ß-lactamase (MBL), and a cumulative 84.2% carried any non-intrinsic ß-lactamase [i.e., not Pseudomonas-derived cephalosporinase (PDC) or OXA-50-like]. Of the 145 CZA-S+C/T-NS isolates, 26.2% carried an extended-spectrum ß-lactamase (ESBL) and no carbapenemase, 17.9% carried a serine-carbapenemase, and 42.1% were negative for non-intrinsic ß-lactamases. Of 98 CZA-NS+C/T-S isolates, 34.7% carried mutations previously described as causing an upregulation of the MexAB-OprM efflux pump, while only 9.2% carried a non-intrinsic ß-lactamase, and no resistance mechanism was identified in 29.6% of these isolates. MBLs were present in most isolates NS to both agents. More than half of the CZA-S+C/T-NS isolates carried serine ß-lactamases. The most frequently identified resistance mechanism identified in CZA-NS+C/T-S isolates was a marker indicating the upregulation of MexAB-OprM. No mechanism was identified that is thought to support resistance to these agents in numerous isolates. This may be due in part to the fact that whole genome sequencing (WGS) cannot directly measure gene expression of chromosomal resistance mechanisms.


Assuntos
Antibacterianos , Compostos Azabicíclicos , Ceftazidima , Cefalosporinas , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa , Tazobactam , beta-Lactamases , Ceftazidima/farmacologia , Compostos Azabicíclicos/farmacologia , Cefalosporinas/farmacologia , Tazobactam/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , beta-Lactamases/genética , beta-Lactamases/metabolismo , Humanos , Sequenciamento Completo do Genoma , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
7.
Artigo em Chinês | MEDLINE | ID: mdl-39223041

RESUMO

Objective: To explore the risk factors of neck work-related musculoskeletal disorders (WMSDs) among automobile manufacturing enterprise workers, and construct the risk prediction model. Methods: In May 2022, a cluster convenience sampling method was used to selet all front-line workers from an automobile manufacturing factory in Xiangyang City as the research objects. And a questionnaire survey was conducted using the modified Musculoskeletal Disorders Questionnaire to analyze the occurrence and exposure to risk factors of neck WMSDs. Logistic regression was used to analyze the influencing factors of workers' neck WMSDs symptoms, and Nomogram column charts was used to construct the risk prediction model. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve, the Bootstrap resampling method was used to verify the model, Hosmer-Lemeshow goodness of fit test was used to evaluate the model, and the Calibration curve was drawn. Results: A total of 1783 workers were surveyed, and the incidence of neck WMSDs symptoms was 24.8% (442/1783). Univariate logistic regression showed that age, female, smoking, working in uncomfortable postures, repetitive head movement, feeling constantly stressed at work, and completing conflicting tasks in work could increase the risk of neck WMSDs symptoms in automobile manufacturing enterprise workers (OR=1.37, 95%CI: 1.16-1.62; OR=2.85, 95%CI: 1.56-5.20; OR=1.50, 95%CI: 1.18-1.91; OR=1.18, 95%CI: 1.02-1.37; OR=1.34, 95%CI: 1.04-1.72; OR=1.62, 95%CI: 1.21-2.17; OR=1.48, 95%CI: 1.13-1.92; P<0.05). While adequate rest time could reduce the risk of neck WMSDs symptoms (OR=0.56, 95%CI: 0.52-0.86, P<0.05). The risk prediction model of neck WMSDs of workers in automobile manutacturing factory had good prediction efficiency, and the area under the ROC curve was 0.72 (95%CI: 0.70-0.75, P<0.001) . Conclusion: The occurrence of neck WMSDs symptoms of workers in automobile manufacturing factory is relatively high. The risk prediction model constructed in this study can play a certain auxiliary role in predicting neck WMSDs symptoms of workers in automobile manufacturing enterprise workers.


Assuntos
Automóveis , Doenças Musculoesqueléticas , Doenças Profissionais , Humanos , Feminino , Doenças Musculoesqueléticas/epidemiologia , Doenças Musculoesqueléticas/etiologia , Masculino , Inquéritos e Questionários , Fatores de Risco , Doenças Profissionais/epidemiologia , Adulto , Modelos Logísticos , Pescoço , Indústria Manufatureira , Pessoa de Meia-Idade , Curva ROC
9.
Br Poult Sci ; : 1-7, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39250000

RESUMO

1. This study calculated descriptive statistics for the production traits of two broiler populations: 1) the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF white broilers), including fat and lean lines; and 2) the Guangxi yellow broilers. Their genetic parameters were estimated, including (co)variance components, heritability (h2) and genetic correlations (rg), using the REML method.2. Heritability estimates (h2) for NEAUHLF white broilers ranged from 0.07 to 0.61. Traits with high heritability (h2 >0.3) included body weight at 3, 5 and 7 weeks of age (BW3, BW5, BW7), carcass weight (CW), metatarsal circumference (MeC), liver weight (LW), gizzard weight (GW), spleen weight (SW) and testis weight (TeW), while in Guangxi yellow broilers, heritability estimates ranged from 0.18 to 0.76, with every trait exhibiting high heritability, except for SW (0.18).3. Positive genetic correlations for NEAUHLF were found (rg >0.3, ranging from 0.31 to 0.84) between BW7 and metatarsal length (MeL), MeC, body oblique length (BoL), chest angle (ChA), LW, GW, heart weight (HW) and SW. Genetic correlations between abdominal fat weight (AFW) and BW1, BW3, BW5, CW, MeL, keel length (KeL), BoL and LW were positive (rg >0.3, ranging from 0.31 to 0.58).4. Among the Guangxi population, BW (125 d of age) showed strong positive genetic correlations with all other traits (rg >0.3, ranging from 0.30 to 0.99), while AFW displayed strong positive genetic correlations with leg muscle weight (LeW), CW, BW and thigh diameter (TD) (rg >0.3, ranging from 0.44 to 0.51).5. It was concluded that the characteristics of the two populations were different, which means there is a need to use different strategies when performing the breeding work to improve productivity and efficiency in both broiler populations.

12.
Artigo em Chinês | MEDLINE | ID: mdl-39289960

RESUMO

Objective: To evaluate auditory spatial discrimination capabilities in patients with mild to moderately severe symmetrical sensorineural hearing loss (SNHL) and to compare the impact of different psychophysical testing methods on Minimum Audible Angle (MAA) and test duration. Methods: A total of 105 symmetrical SNHL patients aged from 18 to 60 years old were enrolled from April to July 2023, including 56 males and 49 females. They were divided into three groups based on PTA: mild, moderate, and moderately severe hearing loss, with 35 individuals in each group. Additionally, a control group of 35 individuals with normal hearing was tested, including 18 males and 17 females. Participants underwent four distinct psychophysical discrimination tests: the block up-down, 1-up/1-down, 1-up/2-down, and 1-up/3-down procedures. We recorded the MAA and test duration for each. We employed repeated measures of ANOVA to compare the MAA and test duration across different methods and groups, and Pearson's correlation to assess the relationship between MAA and degree of hearing loss. Results: MAA of sound localization in patients with symmetrical SNHL was significantly positively correlated with the degree of hearing loss (r=0.59, P<0.01). Significant deterioration in MAA was observed as hearing loss progressed to the moderate level (PTA≥35 dBHL, P<0.01). The testing methods significantly influenced MAA and testing duration (F=24.02, P<0.01; F=75.56, P<0.01) and the 1-up/1-down method was the quickest, averaging only (0.69±0.32) mins. Conclusions: The horizontal plane auditory spatial discrimination abilities in patients with symmetrical SNHL is impaired progressively with increasing hearing loss, notably beyond moderate hearing loss levels. Different psychophysical methods influence both MAA and test duration, the quicker 1-up/1-down method is recommended for assessing MAA in symmetrical SNHL patients.


Assuntos
Perda Auditiva Neurossensorial , Localização de Som , Humanos , Masculino , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/fisiopatologia , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Limiar Auditivo
13.
J Dent Res ; : 220345241271078, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39290151

RESUMO

N6,2'-O-dimethyladenosine (m6Am), a common mRNA modification in eukaryotic capped mRNAs, plays a pivotal role in cellular functions and disease progression. However, its involvement in host inflammation remains elusive. Here, we demonstrate that loss of m6Am methyltransferase phosphorylated CTD interacting factor 1 (PCIF1) attenuates periodontal inflammation in whole-body and myeloid lineage-specific knockout mouse models. Pcif1 deletion inhibits macrophage phagocytosis and migration through m6Am-Csf1r signaling. In addition, colony-stimulating factor-1 receptor (CSF1R) is identified as a potential target for the treatment of periodontitis. We thus reveal a previously unrecognized role for PCIF1-mediated m6Am modification in governing macrophage responses and periodontal inflammation.

14.
Zhonghua Zhong Liu Za Zhi ; 46(9): 862-870, 2024 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-39293989

RESUMO

Objective: To analyze epidemiology of gastric cancer five-year survival distribution in Zhejiang population-based cancer registration. Methods: The follow-up data of registrated gastric cancer cases diagnosed from 2008 to 2019 in 22 national cancer registry areas of Zhejiang Province were collected and divided into three diagnostic periods: 2008-2011, 2012-2015 and 2016-2019 to calculate five-year observed survival rates (OSRs), five-year relative survival rates (RSRs) and five-year age-standardized relative survival rates (ARSRs). The distribution of population characteristics (including gender, urban/rural, age group and occupation) and clinical characteristics (including the highest diagnostic institution, sub-site, pathological type and degree of differentiation) of gastric cancer survival rates in each period were analysed. Results: 51 663 new cases of gastric cancer in 2008-2019 in the cancer registration area of Zhejiang Province were included in the analysis, and the ARSR of gastric cancer in 2008-2011, 2012-2015 and 2016-2019 showed an increasing trend (39.2%, 41.3% and 44.7%, respectively). In 2016-2019, the ARSR was similar across gender and urban and rural areas (44.4% for men and 45.7% for women; 44.9% in urban areas and 44.2% in rural areas); Among people with different occupations, the ARSR was highest among business and service workers (55.3%), the agriculture, forestry, animal husbandry and fisheries, water conservancy production workers and domestic workers were lower (41.5% and 43.2%, respectively). The highest diagnostic institution was the provincial hospital with a higher gastric cancer survival rate (47.0%) than the municipal (43.4%) and district (43.6%) levels. The ARSR for gastric cancer was relatively high in the lesser curvature (59.7%), pylorus (50.4%), antrum (49.3%), and greater curvature (48.7%), and lowest in cardia (38.9%). Among the major pathological types, adenocarcinoma (NOS) had an ARSR of 48.1%, mucinous adenocarcinoma 41.3%, imprinted cell carcinoma 39.4%, and squamous carcinoma 33.4%. The ARSR for highly differentiated, moderately differentiated, poorly differentiated and undifferentiated gastric cancers were 80.6%, 57.9%, 43.2% and 36.8%, respectively. Conclusion: The 5-year survival rate of gastric cancer in Zhejiang Province is high and on the rise, with similar survival rates in different genders, urban and rural areas, and significant differences in the survival rates of gastric cancer patients with different occupational groups, highest diagnostic institutions, tumour sub-sites, pathological types and differentiation degrees.


Assuntos
Sistema de Registros , População Rural , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/epidemiologia , China/epidemiologia , Feminino , Masculino , Taxa de Sobrevida , População Rural/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/epidemiologia , População Urbana/estatística & dados numéricos , Adulto , Prevalência , Análise de Sobrevida
15.
Animal ; 18(10): 101202, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-39270357

RESUMO

Nitrogen (N) utilisation efficiency (NUE, milk N yield [g/d]/N intake [g/d]) is an important performance indicator in dairy farming. Determining the NUE-associated blood metabolite profile will contribute to the optimisation of nutritional strategies to further improve NUE among dairy cows. Here, 20 primiparous lactating cows with days in milk ranging from 95 to 115 days were selected from a total of 1 221 cows. Each cow's N intake and milk N yield were measured for 7 days. Subsequently, blood samples were collected before morning feeding. Based on analysis and calculations, cows were retrospectively classified into two groups based on their NUE values, namely, a low NUE group (LNUE, NUE = 24.8 ± 1.6%, n = 10, mean ± SD) and a high NUE group (HNUE, NUE = 35.2 ± 1.7%, n = 10, mean ± SD). Plasma samples were selected from six cows in each group for metabolomics and amino acid profiling. Among the 41 differential metabolites (DMs) identified in the metabolomic analysis, sucrose, MG(0:0/22:1(13Z)/0:0), 2-amino-6-hydroxyhexanoic acid, and L-glutamine exhibited significant correlations with NUE, milk yield, and BW (P < 0.05). Moreover, the five differential amino acids and amino acid metabolites (DAAs) identified in the amino acid profiling and 5 of the 6 differential amino acids and amino acid conjugates identified by plasma metabolomics were found to be less abundant in the HNUE group (P < 0.05). Specifically, there was a 39.4% decrease in L-arginine content and a 29.2% decrease in L-glutamine content (P < 0.05). Pathway analysis indicated that the DMs and DAAs were mainly involved in arginine biosynthesis, glutathione metabolism, arginine and proline metabolism, and tryptophan metabolism (pathway impact > 0.1). These results provided new insights into the new blood metabolite profile associated with NUE in dairy cows. These new insights can provide foundational information for the formulation of new strategies to further enhance NUE in dairy cows.

16.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(9): 863-868, 2024 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-39266488

RESUMO

Patients with SARS-CoV-2 infection often exhibit significant changes in T cells, particularly a reduction in CD4+T and CD8+T cells in peripheral blood, which has become a key feature of severe respiratory infection. These immune changes in T lymphocytes are closely associated with disease progression, but the specific mechanisms remain unclear and warrant further investigation. This paper reviewed the changes in the number and function of T cells in respiratory viral infections, with a focus on SARS-CoV-2, and summarized related therapeutic explorations. We believe that improving and enhancing the number and function of T lymphocytes in infected hosts is a promising strategy for the treatment of respiratory viral infections, although more systematic and in-depth scientific research is still needed.


Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/imunologia , SARS-CoV-2/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T/imunologia
17.
Eur Rev Med Pharmacol Sci ; 28(17): 4226, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39297596

RESUMO

The article "Influence of 12 weeks of basketball training on college students' heart function" by Z.-T. Yang, S.-W. Kim, Y.-S. Kim, X. Tang, H. Li, E.-L. Wang, published in Eur Rev Med Pharmacol Sci 2023; 27 (14): 6474-6479 DOI: 10.26355/eurrev_202307_33117-PMID: 37522658 has been retracted by the Editor in Chief. Due to third-party concerns about potential misquotations, the Editor-in-Chief has initiated an investigation to verify the validity of the allegations. The journal's assessment has shown that all references cited were not relevant to the text. The authors have been contacted to address the issues but only provided an updated list of references without a satisfactory explanation for the mistake. In light of the absence of a valid justification and the substantial misquotations throughout the text, the Editor-in-Chief has decided to retract the manuscript. The authors have been informed about the retraction but remained unresponsive. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/33117.

18.
Phys Rev Lett ; 133(10): 106401, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39303246

RESUMO

Understanding electron-phonon coupling in noncentrosymmetric materials is critical for controlling the internal fields which give rise to Rashba interactions. We apply time- and angle-resolved photoemission spectroscopy (trARPES) to study coherent phonons in the surface and bulk regions of the polar semiconductor BiTeCl. Aided by ab initio calculations, our measurements reveal the coupling of out-of-plane A_{1} modes and an in-plane E_{2} mode. By considering how these modes modulate the electric dipole moment in each unit cell, we show that the polar A_{1} modes are more effectively screened in the metallic surface region, while the nonpolar E_{2} mode couples in both regions. In addition to informing strategies to optically manipulate Rashba interactions, this Letter has broader implications for the behavior of electron-phonon coupling in systems characterized by inhomogeneous dielectric environments.

19.
Physiol Res ; 73(4): 565-576, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39264078

RESUMO

The endothelial-mesenchymal transition (EndMT) of endothelial progenitor cells (EPCs) plays a notable role in pathological vascular remodeling. Emerging evidence indicated that long non-coding RNA-regulator of reprogramming (linc-ROR) can promote epithelial-mesenchymal transition (EMT) in a variety of cancer cells. Nevertheless, the function of linc-ROR in EPC EndMT has not been well elucidated. The present study investigated the effect and possible mechanisms of function of linc-ROR on the EndMT of EPCs. A linc-ROR overexpression lentiviral vector (LV linc-ROR) or a linc-ROR short hairpin RNA lentiviral vector (LV-shlinc-ROR) was used to up or downregulate linc-ROR expression in EPCs isolated from human umbilical cord blood. Functional experiments demonstrated that LV-linc-ROR promoted the proliferation and migration of EPCs, but inhibited EPC angiogenesis in vitro. In the meantime, reverse transcription-quantitative PCR and western blotting results showed that the expression of the endothelial cell markers vascular endothelial-cadherin and CD31 was decreased, while the expression of the mesenchymal cell markers ?-smooth muscle actin and SM22? was increased at both mRNA and protein levels in LV-linc-ROR-treated EPCs, indicating that linc-ROR induced EPC EndMT. Mechanistically, the dual-luciferase reporter assay demonstrated that microRNA (miR/miRNA)-145 was a direct target of linc-ROR, and miR-145 binds to the 3'-untranslated region of Smad3. Moreover, LV-shlinc-ROR increased the expression of miR-145, but decreased the expression of Smad3. In conclusion, linc-ROR promotes EPC EndMT, which may be associated with the miR-145/Smad3 signaling pathway. Keywords: Endothelial progenitor cells, Endothelial to mesenchymal transition, Linc-ROR, MiR-145, Atherosclerosis.


Assuntos
Células Progenitoras Endoteliais , Transição Epitelial-Mesenquimal , MicroRNAs , RNA Longo não Codificante , Transdução de Sinais , Proteína Smad3 , MicroRNAs/metabolismo , MicroRNAs/genética , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Células Progenitoras Endoteliais/metabolismo , Proteína Smad3/metabolismo , Proteína Smad3/genética , Células Cultivadas , Movimento Celular/fisiologia , Proliferação de Células , Transição Endotélio-Mesênquima
20.
ESMO Open ; 9(9): 103682, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39241496

RESUMO

BACKGROUND: QL1701 is a proposed biosimilar to the reference trastuzumab (Herceptin®). This trial compared the efficacy and safety of QL1701 with the reference trastuzumab in first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. MATERIALS AND METHODS: This randomized, double-blinded, parallel-controlled, phase III equivalence trial was conducted in 73 centers in China. Eligible patients with histologically or cytologically diagnosed HER2-positive metastatic breast cancer were randomly assigned (1 : 1) to receive either QL1701 or reference trastuzumab in combination with docetaxel (every 3 weeks) for eight cycles as the first-line treatment. Then, in patients with objective responses or stable disease, the QL1701 or reference trastuzumab with or without docetaxel was maintained for totally up to 12 months if tolerated. The primary endpoint was 24-week objective response rate (ORR) assessed by an independent review committee (IRC). The equivalence margin was 0.80-1.25 with a 90% confidence interval (CI) for the ORR ratio (QL1701 to reference trastuzumab). RESULTS: Between 29 April 2020 and 15 March 2022, 474 patients were randomized, and 473 received either QL1701 (n = 236) or reference trastuzumab (n = 237). The risk ratio for 24-week ORR was 1.07 (90% CI 0.94-1.21). The 90% CI fell within the pre-specified equivalence margin of 0.80-1.25. The 24-week ORR assessed by IRC was 59.7% (95% CI 53.2% to 66.1%) versus 56.1% (95% CI 49.5% to 62.5%) in QL1701 and the reference trastuzumab, respectively. As of 12 April 2023, there were no notable differences in progression-free survival (median: 8.3 versus 8.4 months) and overall survival (1-year rate: 95.1% versus 93.3%) between the two groups. Safety, pharmacokinetic (PK), and immunogenicity profiles were similar between the two groups. CONCLUSION: QL1701 demonstrated equivalent efficacy and similar safety to the reference trastuzumab when combined with docetaxel in the first-line treatment of patients with HER2-positive metastatic breast cancer, with similar PK and immunogenicity profiles.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Medicamentos Biossimilares , Neoplasias da Mama , Docetaxel , Receptor ErbB-2 , Trastuzumab , Humanos , Trastuzumab/uso terapêutico , Trastuzumab/farmacologia , Docetaxel/uso terapêutico , Docetaxel/farmacologia , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Método Duplo-Cego , Adulto , Medicamentos Biossimilares/uso terapêutico , Medicamentos Biossimilares/farmacologia , Medicamentos Biossimilares/administração & dosagem , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Idoso
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