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Floral patterns are unique to rice and contribute significantly to its reproductive success. SL1 encodes a C2H2 transcription factor that plays a critical role in flower development in rice, but the molecular mechanism regulated by it remains poorly understood. Here, we describe interactions of the SL1 with floral homeotic genes, SPW1, and DL in specifying floral organ identities and floral meristem fate. First, the sl1 spw1 double mutant exhibited a stamen-to-pistil transition similar to that of sl1, spw1, suggesting that SL1 and SPW1 may located in the same pathway regulating stamen development. Expression analysis revealed that SL1 is located upstream of SPW1 to maintain its high level of expression and that SPW1, in turn, activates the B-class genes OsMADS2 and OsMADS4 to suppress DL expression indirectly. Secondly, sl1 dl displayed a severe loss of floral meristem determinacy and produced amorphous tissues in the third/fourth whorl. Expression analysis revealed that the meristem identity gene OSH1 was ectopically expressed in sl1 dl in the fourth whorl, suggesting that SL1 and DL synergistically terminate the floral meristem fate. Another meristem identity gene, FON1, was significantly decreased in expression in sl1 background mutants, suggesting that SL1 may directly activate its expression to regulate floral meristem fate. Finally, molecular evidence supported the direct genomic binding of SL1 to SPW1 and FON1 and the subsequent activation of their expression. In conclusion, we present a model to illustrate the roles of SL1, SPW1, and DL in floral organ specification and regulation of floral meristem fate in rice.
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Flores , Regulação da Expressão Gênica de Plantas , Meristema , Oryza , Proteínas de Plantas , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Meristema/genética , Meristema/crescimento & desenvolvimento , Meristema/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Flores/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Plantas Geneticamente Modificadas , MutaçãoRESUMO
BACKGROUND: Little s antigen is mainly defined by a single nucleotide polymorphism at c.143C (p.Thr48) on the GYPB gene. Several variants on GYPB can alter the expression of s antigen. The aim of this study was to investigate the molecular basis of variant s antigen expression in the Chinese population. STUDY DESIGN AND METHODS: A total of 4983 whole blood samples were collected to screen the individuals with discrepant s typing results using two different monoclonal anti-s. Then, the sequence of GYPB exon 4 was analyzed by Sanger sequencing. Flow cytometry analysis was performed to quantify s antigen expression on red blood cells (RBCs). In vitro expression study was performed to verify the effect of the GYPB variants identified on the expression of s antigen. RESULTS: Four donors were identified to have discrepant s typing results. Sanger sequencing showed that three donors carried the c.173C > G variant (p.Pro58Arg) specific for sD antigen, the other one carried a novel GYPB (c.160C > T, p.Arg54Cys) variant. Flow cytometry identified a partial and weak expression of s antigen on the RBCs of the four donors. Furthermore, in vitro expression study confirmed the effect of the two variants on the s antigen expression. CONCLUSION: The results demonstrated that in addition to p.Thr48, the two extra amino acids p.Arg54 and p.Pro58 are also important for full expression of s antigen. Since the individuals with partial s antigen are at risk for the development of alloanti-s, it is important to select at least two different monoclonal anti-s for correct s typing.
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Antígenos de Grupos Sanguíneos , Glicoforinas , Humanos , Alelos , Glicoforinas/genética , Antígenos de Grupos Sanguíneos/genética , Fenótipo , Eritrócitos/metabolismo , Sistema do Grupo Sanguíneo Rh-Hr/metabolismoRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, relapsing condition wherein biologics have improved disease prognosis but introduced elevated infection susceptibility. Vedolizumab (VDZ) demonstrates unique safety advantages; however, a comprehensive systematic comparison regarding the risk of Clostridioides difficile infection (CDI) between vedolizumab and alternative medications remains absent. METHOD: Medline, Embase, Cochrane, and clinicaltrials.gov registry were comprehensively searched. Pooled estimates of CDI proportion, incidence, pooled risk ratio between ulcerative colitis (UC) and Crohn's disease (CD), vedolizumab and other medications were calculated. Data synthesis was completed in R using the package "meta". RESULTS: Of the 338 studies initially identified, 30 met the inclusion/exclusion criteria. For CDI risk, the pooled proportion was 0.013 (95% CI 0.010-0.017), as well as the pooled proportion of serious CDI was 0.004 (95% CI 0.002-0.008). The comparative pooled risk ratios revealed: UC versus CD at 2.25 (95% CI 1.73-2.92), vedolizumab versus anti-TNF agents at 0.15 (95% CI 0.04-0.63) for UC and 1.29 (95% CI 0.41-4.04) for CD. CONCLUSION: The overall CDI risk in IBD patients exposed to vedolizumab was estimated to be 0.013. An increased risk of CDI was noted in UC patients receiving vedolizumab compared to those with CD. Vedolizumab potentially offers an advantage over anti-TNF agents for UC regarding CDI risk, but not for CD. TRIAL REGISTRATION: The study was registered on the PROSPERO registry (CRD42023465986).
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Anticorpos Monoclonais Humanizados , Infecções por Clostridium , Fármacos Gastrointestinais , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Humanos , Infecções por Clostridium/epidemiologia , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/complicações , Clostridioides difficile , Doença de Crohn/tratamento farmacológico , IncidênciaRESUMO
Particle-enhanced turbidimetric immunoassay (PETIA) is a new measurement procedure for detecting fecal calprotectin (FC). We aimed to investigate the accuracy and clinical performance of PETIA for FC. We assessed the accuracy of PETIA for FC measurements through concordance analysis, Passing-Bablok regression and Bland-Altman analysis, using enzyme-linked immunosorbent assay (ELISA) as the reference. To evaluate the clinical performance of PETIA, the FC levels of individuals with significant and non-significant bowel diseases were compared. The receiver operating characteristic (ROC) analysis was performed to determine the appropriate cut-off value of FC detected by PETIA for discriminating subjects with significant and non-significant colorectal lesions. Of the 413 cases analyzed, 340 (82.3%) were concordant between PETIA and ELISA. No significant discordance was observed. There was a good agreement (y = -7.710+0.957x) between PETIA and ELISA for detecting FC. The FC level detected by PETIA in patients with significant bowel diseases (159.1 [31.3, 821.0] µg/g) was significantly higher than that of subjects with non-significant bowel diseases (10.3 [4.2, 38.5] µg/g) (p < 0.001). The AUC of FC for identifying significant bowel diseases detected by PETIA was 0.82 (p < 0.001). With a cut-off value of 77.6µg/g, the specificity and positive predictive value were 92.2% and 97.1%, respectively. The PETIA for FC measurement showed good clinical performance for detecting bowel diseases.
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BACKGROUND: Parkinson's disease (PD) has been regarded as a disconnection syndrome with functional and structural disturbances. However, as the anatomic determinants, the structural disconnections in PD have yet to be fully elucidated. PURPOSE: To non-invasively construct structural networks based on microstructural complexity and to further investigate their potential topological abnormalities in PD given the technical superiority of diffusion kurtosis imaging (DKI) to the quantification of microstructure. MATERIAL AND METHODS: The microstructural data of gray matter in both the PD group and the healthy control (HC) group were acquired using DKI. The structural networks were constructed at the group level by a covariation approach, followed by the calculation of topological properties based on graph theory and statistical comparisons between groups. RESULTS: A total of 51 patients with PD and 50 HCs were enrolled. Individuals were matched between groups with respect to demographic characteristics (P >0.05). The constructed structural networks in both the PD and HC groups featured small-world properties. In comparison with the HC group, the PD group exhibited significantly altered global properties, with higher normalized characteristic path lengths, clustering coefficients, local efficiency values, and characteristic path lengths and lower global efï¬ciency values (P <0.05). In terms of nodal centralities, extensive nodal disruptions were observed in patients with PD (P <0.05); these disruptions were mainly distributed in the sensorimotor network, default mode network, frontal-parietal network, visual network, and subcortical network. CONCLUSION: These findings contribute to the technical application of DKI and the elucidation of disconnection syndrome in PD.
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Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Imagem de Tensor de Difusão , Substância Cinzenta/diagnóstico por imagemRESUMO
BACKGROUND: There are numerous symptoms related to cancer and its treatments that can affect the psychosomatic health and quality of life of patients with cancer. The use of electronic symptom management systems (ESMSs) can help patients with cancer monitor and manage their symptoms effectively, improving their health-related outcomes. However, patients' adhesion to ESMSs decreases over time, and little is known about their real experiences with them. Therefore, it is necessary to gain a deep understanding of patients' experiences with ESMSs. OBJECTIVE: The purpose of this systematic review was to synthesize qualitative studies on the experiences of patients with cancer using ESMSs. METHODS: A total of 12 electronic databases, including PubMed, Web of Science, Cochrane Library, EBSCOhost, Embase, PsycINFO, ProQuest, Scopus, Wanfang database, CNKI, CBM, and VIP, were searched to collect relevant studies from the earliest available record until January 2, 2024. Qualitative and mixed methods studies published in English or Chinese were included. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement checklist) and the ENTREQ (Enhancing Transparency in Reporting the Synthesis of Qualitative Research) statement were used to improve transparency in reporting the synthesis of the qualitative research. The Critical Appraisal Skills Program (CASP) checklist was used to appraise the methodological quality of the included studies, and a meta-synthesis was conducted to interpret and synthesize the findings. RESULTS: A total of 21 studies were included in the meta-synthesis. The experiences of patients with cancer using ESMSs were summarized into three major categories: (1) perceptions and attitudes toward ESMSs; (2) the value of ESMSs; and (3) barriers, requirements, and suggestions for ESMSs. Subsequently, 10 subcategories emerged from the 3 major categories. The meta-synthesis revealed that patients with cancer had both positive and negative experiences with ESMSs. In general, patients recognized the value of ESMSs in symptom assessment and management and were willing to use them, but they still encountered barriers and wanted them to be improved. CONCLUSIONS: This systematic review provides implications for developing future ESMSs that improve health-related outcomes for patients with cancer. Future research should focus on strengthening electronic equipment and technical support for ESMSs, improving their functional contents and participation forms, and developing personalized applications tailored to the specific needs and characteristics of patients with cancer. TRIAL REGISTRATION: PROSPERO CRD42023421730; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=421730.
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Neoplasias , Humanos , Neoplasias/psicologia , Neoplasias/terapia , Pesquisa Qualitativa , Qualidade de Vida , FemininoRESUMO
INTRODUCTION: To evaluate the effect of 3-dimensional (3D) imaging device on polyp and adenoma detection during colonoscopy. METHODS: In a single-blind, randomized controlled trial, participants aged 18-70 years who underwent diagnostic or screening colonoscopy were consecutively enrolled between August 2019 and May 2022. Each participant was randomized in a 1:1 ratio to undergo either 2-dimensional (2D-3D) colonoscopy or 3D-2D colonoscopy through computer-generated random numbers. Primary outcome included polyp detection rate (PDR) and adenoma detection rate (ADR), defined as the proportion of individuals with at least 1 polyp or adenoma detected during colonoscopy. The primary analysis was intention-to-treat. RESULTS: Of 1,196 participants recruited, 571 in 2D-3D group and 583 in 3D-2D group were finally included after excluding those who met the exclusion criteria. The PDR between 2D and 3D groups was separately 39.6% and 40.5% during phase 1 (odds ratio [OR] = 0.96, 95% confidence interval [CI]: 0.76-1.22, P = 0.801), whereas PDR was significantly higher in 3D group (27.7%) than that of 2D group (19.9%) during phase 2, with a 1.54-fold increase (1.17-2.02, P = 0.002). Similarly, the ADR during phase 1 between 2D (24.7%) and 3D (23.8%) groups was not significant (OR = 1.05, 0.80-1.37, P = 0.788), while ADR was significantly higher in 3D group (13.8%) than that of 2D group (9.9%) during phase 2, with a 1.45-fold increase (1.01-2.08, P = 0.041). Further subgroup analysis confirmed significantly higher PDR and ADR of 3D group during phase 2, particularly in midlevel and junior endoscopists. DISCUSSION: The 3D imaging device could improve overall PDR and ADR during colonoscopy, particularly in midlevel and junior endoscopists. Trial number: ChiCTR1900025000.
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Adenoma , Pólipos do Colo , Neoplasias Colorretais , Humanos , Pólipos do Colo/diagnóstico por imagem , Imageamento Tridimensional , Método Simples-Cego , Colonoscopia/métodos , Adenoma/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagemRESUMO
Polaprezinc (PZ) plays a role in the protection of gastric mucosa and inhibiting Helicobacter pylori (H. pylori) growth in vitro. The objective of this study was to determine the protective effects of PZ on human gastric epithelial cells (GES-1) against H. pylori-induced damage, while also examining heat shock protein 70 (HSP70) as a potential underlying factor in this protection. Our findings revealed that PZ exerted bactericidal effects against H. pylori strains. We also observed that PZ mitigated the H. pylori-induced damage to GES-1 cells by increasing cell viability, reducing LDH release, and decreasing the secretion of pro-inflammatory factors such as MCP-1 and IL-6. Co-culturing PZ with GES-1 cells significantly up-regulated the GES-1 HSP70 expression in both a time and dose-dependent manner. Pre-incubating (for 12 h) or co-culturing (for 24 h) GES-1 cells with PZ reversed the down-regulation of HSP70 in GES-1 cells caused by H. pylori infection. However, when quercetin was used to inhibit the up-regulation of HSP70 in GES-1 cells, the protective effect of PZ on GES-1 cells was significantly reduced. Based on the results of this study, PZ exhibits a protective role on GES-1 cells against H. pylori injury, as well as a direct bactericidal effect on H. pylori. HSP70 is involved in the PZ-driven host cell protection against H. pylori injury. These findings provide insight into alternative strategies for H. pylori treatment.
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Infecções por Helicobacter , Helicobacter pylori , Compostos Organometálicos , Humanos , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP70/farmacologia , Citoproteção , Compostos Organometálicos/metabolismo , Compostos Organometálicos/farmacologia , Células Epiteliais/metabolismo , Infecções por Helicobacter/metabolismo , Mucosa GástricaRESUMO
OBJECTIVES: Although colonoscopy remains the gold standard for determining bowel diseases, it's invasive and expensive. New non-invasive diagnostic methods are urgently needed as an initial screening modality. We aimed to investigate the value of fecal calprotectin (FC) and fecal immunochemical test (FIT) in differentiation of significant and non- significant bowel diseases. METHODS: In this prospective study, consecutive individuals were included if they underwent colonoscopy for symptoms of lower gastrointestinal (GI) tract, positive fecal occult blood test, surveillance for IBD or colorectal cancer (CRC) screening. Diagnostic value of FC and FIT in discriminating significant bowel diseases (advanced neoplasia, active inflammatory bowel diseases or bowel inflammation due to other causes) and non-significant bowel diseases (normal, asymptomatic diverticulum, non-adenomatous polyp, or non-advanced neoplasia) were evaluated. RESULTS: Among 201 individuals included, 107 patients had significant bowel diseases. FC and FIT had an area under the curve (AUC) of 0.722 (95% confidence interval [CI] 0.653-0.792) and 0.797 (95%CI 0.734-0.860), respectively, for determining significant bowel diseases. Combination of FC and FIT predicted significant bowel diseases with an AUC, sensitivity, specificity, and accuracy of 0.832 (95% CI 0.775-0.890), 77.6%, 74.5%, and 76.1%, respectively. Moreover, combination of FC and FIT was more sensitive among patients with lower GI symptoms than asymptomatic individuals (80.8% vs. 74.1%) to identify significant bowel diseases. CONCLUSIONS: A single measurement of FC or FIT is not sufficiently accurate to identify patients with significant bowel disease. However, combination of FC and FIT can help increase the sensitivity, especially in patients with lower GI symptoms.
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Doenças Inflamatórias Intestinais , Humanos , Hemoglobinas , Doenças Inflamatórias Intestinais/diagnóstico , Complexo Antígeno L1 Leucocitário , Estudos ProspectivosRESUMO
MYB genes regulate several different aspects of metabolism and development. However, few studies have reported the involvement of MYBs-CesAs network in the regulation of maize kernel development. In this study, yeast one-hybrid (Y1H) assays and dual-luciferase reporter assays showed that ZmMYB109 activated the expression of ZmCesA5 by directly binding to its promoter. Real-time quantitative PCR (RT-qPCR) and transcriptome analyses showed that ZmMYB109 expression increased in ZmCesA5-OE kernels and decreased in ZmCesA5-KO kernels. Overexpression of ZmCesA5 produced heavier kernels, whereas loss of function of ZmCesA5 affected starch and sucrose metabolism, resulting in weight reduction of the maize kernels. Collectively, these findings suggest that a new network containing MYB109-ZmCesA5 is involved in kernel development.
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Amido , Zea mays , Metabolismo dos Carboidratos , Perfilação da Expressão Gênica , Amido/metabolismo , Zea mays/metabolismoRESUMO
OBJECTIVE: This study explores the willingness of older adults to use smartphones and improve their digital skills and encourages nursing to actively participate in bridging the digital divide. METHODS: Subject analysis was used to conduct qualitative research, and 23 older adults were interviewed. RESULTS: We identified four themes: (1) the current situation of smartphone use; (2) the digital dilemma of smartphone use; (3) social support for digital skills; and (4) the willingness to learn digital skills. Older adults in China are willing to accept and use smartphones for simple operations, and peer learning may be an effective way to improve their digital skills. CONCLUSION: Community support is necessary to develop the digital skills of older adults with smartphones and reduce the digital divide to the greatest extent possible. Nursing may play a role in promoting digital inclusion for older adults.
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População do Leste Asiático , Smartphone , Humanos , Idoso , Aprendizagem , Apoio Social , Pesquisa QualitativaRESUMO
BACKGROUND: Signaling lymphocytic activation molecule family-7 (SLAMF7) functions as an immune checkpoint molecule on macrophages in antitumor immunity. However, its role in bacterial infection remains largely unknown. METHODS: Bone marrow-derived macrophages (BMDMs) isolated from wild-type (WT) or SLAMF7 knockout (KO) mice were infected with bacteria or treated with lipopolysaccharide/interferon-γ to investigate the expression and function of SLAMF7 in macrophage polarization. A Pseudomonas aeruginosa keratitis murine model was established to explore the effect of SLAMF7 on P. aeruginosa keratitis using WT vs SLAMF7 KO mice, or recombinant SLAMF7 vs phosphate-buffered saline-treated mice, respectively. RESULTS: SLAMF7 expression was enhanced on M1-polarized or bacterial-infected macrophages, and infiltrating macrophages in P. aeruginosa-infected mouse corneas. SLAMF7 promoted M2 polarization by inducing STAT6 activation. In vivo data showed that SLAMF7 KO aggravated, while treatment with recombinant SLAMF7 alleviated, corneal inflammation and disease severity. In addition, blockage of M2 polarization by Arg-1 inhibitor abrogated the effect of recombinant SLAMF7 in disease progression. CONCLUSIONS: SLAMF7 expression in macrophages was induced upon M1 polarization or bacterial infection and alleviated corneal inflammation and disease progression of P. aeruginosa keratitis by promoting M2 polarization. These findings may provide a potential strategy for the treatment of P. aeruginosa keratitis.
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Córnea , Inflamação , Ceratite , Macrófagos/citologia , Família de Moléculas de Sinalização da Ativação Linfocitária/genética , Animais , Polaridade Celular , Córnea/fisiopatologia , Progressão da Doença , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infecções por Pseudomonas , Pseudomonas aeruginosa , Transdução de SinaisRESUMO
OBJECTIVES: The present study was designed to investigate the effects of microRNA-21 (miR-21) on orthodontic tooth movement. METHODS: The orthodontic tooth movement model was established in C57BL/6 and miR-21-/- mice with or without implantation of activated T cells. Histological and histomorphometrical analyses were performed by hematoxylin-eosin staining. Tartrate-resistant acid phosphate staining was used to analyze the osteoclast numbers during tooth movement. Enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and immunohistochemistry analysis were used to examine the expression of RANKL and OPG. RESULTS: In miR-21-/- mice, the distance of tooth movement was retarded, the osteoclast number was decreased, and serum RANKL expression was strongly reduced. MiR-21 promoted the secretion of RANKL from activated T cells. Furthermore, activated T cells could partially rescue the decreased orthodontic tooth movement distance in miR-21-/- mice. MiR-21 was shown to promote orthodontic tooth movement by modulating the RANKL/OPG balance in T cells. CONCLUSIONS: The impact of miR-21 on tooth movement was better elucidated, furthering our understanding of its role and clinical applications in orthodontics.
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MicroRNAs/genética , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Linfócitos T/metabolismo , Técnicas de Movimentação Dentária , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoclastos/citologiaRESUMO
Photobiomodulation (PBM) has been shown to improve wound healing by promoting mesenchymal stem cell migration and proliferation. However, it remains unknown whether an 808-nm diode laser can influence human gingival mesenchymal stem cells (HGMSCs), and which dose this works well. In the present study, it was found that PBM could promote the migration of HGMSCs but not the proliferation. Furthermore, PBM could activate mitochondrial ROS, which could elevate the phosphorylation levels of JNK and IKB in HGMSCs, and further activate NF-κB as the nuclear translocation of p65 is elevated. Taken together, these present results indicate that PBM might promote cell migration via the ROS/JNK/NF-κB pathway.
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Movimento Celular/efeitos da radiação , Gengiva/fisiologia , Gengiva/efeitos da radiação , Lasers Semicondutores/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Células-Tronco Mesenquimais/citologia , Cicatrização/efeitos da radiação , Gengiva/citologia , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Células-Tronco Mesenquimais/efeitos da radiação , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação , NF-kappa B/metabolismo , Fosforilação/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismoRESUMO
Wound healing can be divided into different phases, and timely initiation and cessation of these stages is key to successful wound healing; otherwise, scar tissue forms in the wounded area. Connexins (Cxs) were confirmed to influence scar formation, and Cx43, an indispensable member of the Cx family, was shown to be involved in this process. Our study investigated the regulatory role of Cx43 in scar formation and the possible cell signalling pathways. We established oral mucosa and skin wound healing models in C57BL/6J mice. RT-PCR, western blotting, immunohistochemistry and immunofluorescence were used to examine the expression of ECM components and key proteins in cell signalling pathways (TGF-ß1, Smad2/3, Cx43, Erk1/2 MMP-1 and collagen III). After injury, buccal mucosa wounds healed with no scar, whereas skin wounds healed with an evident scar. Nevertheless, TGF-ß1 expression gradually increased by the 5th day after injury; Cx43 expression showed a similar response, with a progressive increase in the skin and a peak on day 14. In contrast, TGF-ß1 and Cx43 expression in the oral mucosa remained low. The high level of TGF-ß1 increased p-Smad2/3 levels and then induced Cx43, whereas increased expression of Cx43 antagonised the phosphorylation of Erk1/2, a protein downstream of Cx43, which affected MMP-1 synthesis. MMP-1 deficiency led to collagen III accumulation and facilitated scar formation. We demonstrated that TGF-ß1-induced Cx43 promotes scar formation via the Erk/MMP-1/collagen III pathway.
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Conexina 43 , Fator de Crescimento Transformador beta1 , Animais , Cicatriz , Colágeno , Humanos , Metaloproteinase 1 da Matriz/genética , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Patients with chronic hepatitis B usually exhibit a low response to treatment with interferon α (IFN-α). An alternative approach to increase the response rate of IFN-α might be to immunologically stimulate the host with glucocorticoids (GCs) before treatment with IFN-α, but the underlying mechanism remains unclear. We hypothesized that the GCs enhance IFN signaling by inducing S-adenosylmethionine (AdoMet) when hepatitis B virus (HBV) replication was effectively suppressed by IFN-α. Here, we investigated the effect of GCs and IFN-α on AdoMet production and methionine adenosyltransferase 1A (MAT1A) expression in vitro. Furthermore, we determined whether post-transcriptional regulation is involved in HBV-repressed MAT1A expression and AdoMet production induced by dexamethasone (Dex). We found that AdoMet homeostasis was disrupted by Dex and that Dex directly regulated MAT1A expression by enhancing the binding of the glucocorticoid receptor (GR) to the glucocorticoid-response element (GRE) of the MAT1A promoter. HBV reduced AdoMet production by increasing methylation at GRE sites within the MAT1A promoter. The X protein of hepatitis B virus led to hypermethylation in the MAT1A promoter by recruiting DNA methyltransferase 1, and it inhibited GR binding to the GRE in the MAT1A promoter. Dex could increase an antiviral effect by inducing AdoMet production via a positive feedback loop when HBV is effectively suppressed by IFN-α, and the mechanism that involves Dex-induced AdoMet could increase STAT1 methylation rather than STAT1 phosphorylation. These findings provide a possible mechanism by which GC-induced AdoMet enhances the antiviral activity of IFN-α by restoring STAT1 methylation in HBV-infected cells.
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Glucocorticoides/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Interferon-alfa/farmacologia , S-Adenosilmetionina/metabolismo , Fator de Transcrição STAT1/metabolismo , Antivirais/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , DNA (Citosina-5-)-Metiltransferase 1 , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA/efeitos dos fármacos , Dexametasona/farmacologia , Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Vírus da Hepatite B/fisiologia , Humanos , Immunoblotting , Metionina Adenosiltransferase/genética , Metionina Adenosiltransferase/metabolismo , Metilação/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Receptores de Glucocorticoides/metabolismo , Elementos de Resposta/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacosRESUMO
Objective: The objective is to elucidate the collaboration and current research status in the pediatric field of fNIRS using bibliometric analysis, and to discuss future directions. Method: Bibliometric analysis was conducted on publications related to pediatric fNIRS research published before June 2024 in the Web of Science Core Collection using VOSviewer software and R language. Results: A total of 761 documents were retrieved, published by 2,686 authors from 893 institutions across 44 countries in 239 journals. The number of publications has significantly increased since 2012. The United States is the country with the highest number of publications, University College London is the institution with the most publications, Lloyd-Fox Sarah is the author with the most publications and significant influence, and "Neurophotonics" is the journal with the most publications. The current hotspots mainly involve using fNIRS to study executive functions and autism spectrum disorders in children. Conclusion: The study provides useful reference information for researchers by analyzing publication numbers, collaborative networks, publishing journals, and research hotspots. In the future, there should be an emphasis on enhancing interdisciplinary and international collaboration to collectively dedicate efforts toward the advancement of fNIRS technology and the standardization of research.
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Medulloblastoma (MB) is a primary brain malignancy. However, updated epidemiological data and long-term outcomes are lacking.The clinical and epidemiological datasets of patients with MB in the current study were obtained from the Surveillance, Epidemiology, and End Results (SEER) databases. Joinpoint regression models were used to assess the rate of changes in the incidence, prevalence, and treatment trends in patients with MB. Cox hazard and competition risk model analyses were used to assess overall survival (OS) and cancer-specific survival (CSS).The age-adjusted incidence of MB remained relatively stable at 0.15 per 100,000 individuals in 2019. The annual percentage change (APC) of females remained stable, whereas that of males increased over time. The 20-year limited-duration prevalence of patients with MB increased significantly from 0.00016 % in 1999 to 0.00203 % in 2018. Patients aged 5-19 years accounted for 46.7 % of all age groups, and the trend for the three treatments was increased. Average annual percentage change (AAPC) for the chemotherapy group was increased in patients aged 20 + years MB [AAPC = 2.66 (95 % CI 0.93-6.31)]. Multivariate analysis revealed that OS and CSS varied significantly according to age, year of diagnosis, histology, stage, surgery, and radiotherapy. Subgroup analysis showed that chemotherapy was associated with a favorable prognosis in high-risk groups.The incidence of MB remained relatively stable, and its prevalence increased significantly. This current population-based study further identified the prognostic factors in patients with MB. Moreover, the use of chemotherapy was associated with better survival in high-risk groups.
Assuntos
Neoplasias Cerebelares , Meduloblastoma , Programa de SEER , Humanos , Meduloblastoma/mortalidade , Meduloblastoma/epidemiologia , Meduloblastoma/terapia , Feminino , Masculino , Adolescente , Criança , Pré-Escolar , Adulto Jovem , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Cerebelares/mortalidade , Neoplasias Cerebelares/epidemiologia , Neoplasias Cerebelares/terapia , Incidência , Lactente , Prevalência , IdosoRESUMO
PURPOSE: To develop an in-depth understanding of the meaning of symptoms in the context of how women with stage I-III breast cancer in China cope with the effects of primary and adjuvant therapies for breast cancer. METHOD: A qualitative descriptive approach was used. A purposive sample of women diagnosed with stage I-III breast cancer were recruited from the "Be Resilient to Breast Cancer" study between November 2023 and March 2024. Data was collected from in person interviews using a semi-structured interview guide. Interviews were audio-recorded and transcribed verbatim. The framework analysis method was used to generate codes and themes. RESULTS: A sample of 17 women with breast cancer agreed to participate. The average age was 50.1 years (SD = 8.45), and the majority (65%) had stage III. The overarching theme was Confronting Physical and Psychological Symptoms. The four themes explaining the experience were Changed Identity, Uncertainty, Finding Meaning and Seeking Support and Solace. Changed Identity and Uncertainty reflected the challenges of coping with multiple symptoms from the treatment. The themes of Finding Meaning and Seeking Support and Solace captured how women adapted a positive perspective to cope with the experience. CONCLUSIONS: This study contributed to the evidence of the integration of the symptom experience in coping with breast cancer treatment in the context of a collectivist Chinese culture. It enhanced the understanding of the physical and psychological symptom experience of curative intent breast cancer therapy and offered insight into how women from China cope in early survivorship.
RESUMO
PURPOSE: The aim of this study was to examine the level of health-related quality of life (HRQOL) of lung cancer patients receiving immune checkpoint inhibitors (ICIs) and analyze its influencing factors. METHOD: A cross-sectional study was conducted. From April 2022 to March 2023, 560 lung cancer patients receiving ICIs at three medical bases in Guangzhou, China were recruited using a convenient sampling method. A general information questionnaire, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), the Social Support Rating Scale (SSRS) and the Medical Coping Modes Questionnaire (MCMQ) were used for collecting data on sociodemographic and clinical characteristics, HRQOL, social support and medical coping mode. A descriptive analysis was conducted to describe HRQOL. Multiple regression analysis was applied to determine the factors influencing HRQOL. RESULTS: For lung cancer patients receiving ICIs, the mean score of HRQOL was 59.21 ± 19.86. Multivariate analysis indicated that acceptance-resignation coping mode (ß = -0.37, P < 0.01), Eastern Cooperative Oncology Group (ECOG) score (ß = -0.35, P < 0.01), combination of chemotherapy and/or bevacizumab (ß = -0.14, P < 0.01), and subjective support (ß = 0.07, P = 0.04) all contributed to 42.7% of the variance in HRQOL of the patients receiving ICIs. CONCLUSIONS: It is imperative to address and resolve the HRQOL issue for lung cancer patients receiving ICIs. The findings suggest nurse practitioners should be aware of a variety of factors that influence HRQOL and provide tailored inventions to patients as early as possible to help them achieve better HRQOL.