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1.
Mol Microbiol ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38725184

RESUMO

The hmuR operon encodes proteins for the uptake and utilization of heme as a nutritional iron source in Bradyrhizobium japonicum. The hmuR operon is transcriptionally activated by the Irr protein and is also positively controlled by HmuP by an unknown mechanism. An hmuP mutant does not express the hmuR operon genes nor does it grow on heme. Here, we show that hmuR expression from a heterologous promoter still requires hmuP, suggesting that HmuP does not regulate at the transcriptional level. Replacement of the 5' untranslated region (5'UTR) of an HmuP-independent gene with the hmuR 5'UTR conferred HmuP-dependent expression on that gene. Recombinant HmuP bound an HmuP-responsive RNA element (HPRE) within the hmuR 5'UTR. A 2 nt substitution predicted to destabilize the secondary structure of the HPRE abolished both HmuP binding activity in vitro and hmuR expression in cells. However, deletion of the HPRE partially restored hmuR expression in an hmuP mutant, and it rescued growth of the hmuP mutant on heme. These findings suggest that the HPRE is a negative regulatory RNA element that is suppressed when bound by HmuP to express the hmuR operon.

2.
Sci Rep ; 14(1): 11741, 2024 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-38778035

RESUMO

Communication is crucial in constructing the relationship between students and advisers, ultimately bridging interpersonal interactions. Only a few studies however explore the communication between postgraduate students and advisers. To fill the gaps in the empirical researches, this study uses functional near-infrared spectroscopy (FNIRS) techniques to explore the neurophysiology differences in brain activation of postgraduates with different adviser-advise relationships during simulated communication with their advisers. Results showed significant differences in the activation of the prefrontal cortex between high-quality and the low-quality students during simulating and when communicating with advisers, specifically in the Broca's areas, the frontal pole, and the orbitofrontal and dorsolateral prefrontal cortices. This further elucidated the complex cognitive process of communication between graduate students and advisers.


Assuntos
Comunicação , Córtex Pré-Frontal , Estudantes , Humanos , Masculino , Feminino , Estudantes/psicologia , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Relações Interpessoais , Espectroscopia de Luz Próxima ao Infravermelho , Adulto , Adulto Jovem , Mapeamento Encefálico , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem
3.
Cancer Nurs ; 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704740

RESUMO

BACKGROUND: Patients with breast cancer have an estimated 14% to 60% risk of developing lymphedema after treatment. Self-management behavior strategies regarding lymphedema are essential in preventing and alleviating the severity of lymphedema. OBJECTIVE: The aim of this study was to evaluate qualitative research evidence on the potential influencing factors for self-management behaviors of lymphedema in patients with breast cancer. METHODS: A systematic search of 10 electronic databases was conducted to identify qualitative studies on patient experience of lymphedema self-management. The following databases were included and appraised using the Joanna Briggs Institute Critical Appraisal Checklist: Cochrane Library, PubMed, EMBASE, Web of Science, PsycINFO, Scopus, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Infrastructure, Wanfang Med Online, and Chinese Biomedical Database. RESULTS: The literature search yielded 5313 studies, of which only 22 qualitative studies fulfilled the eligibility criteria. Five synthesized findings were derived encompassing personal characteristics, personal knowledge and experience, personal health beliefs, self-regulation skills and abilities, and social influences and support. CONCLUSIONS: Patients with breast cancer are confronted with many challenges when performing self-management of lymphedema. Therefore, it is important to recognize potential facilitators and barriers to further offer practical recommendations that promote self-management activities for lymphedema. IMPLICATIONS FOR PRACTICE: Healthcare professionals should receive consistent training on lymphedema management. On the basis of individual patient characteristics, tailored education and support should be provided, including transforming irrational beliefs, and improving related knowledge and skills, with the aim to promote self-management behaviors with respect to lymphedema.

4.
J Nanobiotechnology ; 22(1): 215, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693585

RESUMO

Stem cells (SCs) have been used therapeutically for decades, yet their applications are limited by factors such as the risk of immune rejection and potential tumorigenicity. Extracellular vesicles (EVs), a key paracrine component of stem cell potency, overcome the drawbacks of stem cell applications as a cell-free therapeutic agent and play an important role in treating various diseases. However, EVs derived from two-dimensional (2D) planar culture of SCs have low yield and face challenges in large-scale production, which hinders the clinical translation of EVs. Three-dimensional (3D) culture, given its ability to more realistically simulate the in vivo environment, can not only expand SCs in large quantities, but also improve the yield and activity of EVs, changing the content of EVs and improving their therapeutic effects. In this review, we briefly describe the advantages of EVs and EV-related clinical applications, provide an overview of 3D cell culture, and finally focus on specific applications and future perspectives of EVs derived from 3D culture of different SCs.


Assuntos
Técnicas de Cultura de Células em Três Dimensões , Vesículas Extracelulares , Células-Tronco , Vesículas Extracelulares/metabolismo , Humanos , Células-Tronco/citologia , Células-Tronco/metabolismo , Animais , Técnicas de Cultura de Células em Três Dimensões/métodos , Técnicas de Cultura de Células/métodos
5.
JCI Insight ; 9(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38646935

RESUMO

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, with F508del being the most prevalent mutation. The combination of CFTR modulators (potentiator and correctors) has provided benefit to CF patients carrying the F508del mutation; however, the safety and effectiveness of in utero combination modulator therapy remains unclear. We created a F508del ferret model to test whether ivacaftor/lumacaftor (VX-770/VX-809) therapy can rescue in utero and postnatal pathologies associated with CF. Using primary intestinal organoids and air-liquid interface cultures of airway epithelia, we demonstrate that the F508del mutation in ferret CFTR results in a severe folding and trafficking defect, which can be partially restored by treatment with CFTR modulators. In utero treatment of pregnant jills with ivacaftor/lumacaftor prevented meconium ileus at birth in F508del kits and sustained postnatal treatment of CF offspring improved survival and partially protected from pancreatic insufficiency. Withdrawal of ivacaftor/lumacaftor treatment from juvenile CF ferrets reestablished pancreatic and lung diseases, with altered pulmonary mechanics. These findings suggest that in utero intervention with a combination of CFTR modulators may provide therapeutic benefits to individuals with F508del. This CFTR-F508del ferret model may be useful for testing therapies using clinically translatable endpoints.


Assuntos
Aminofenóis , Aminopiridinas , Benzodioxóis , Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Furões , Quinolonas , Animais , Feminino , Gravidez , Aminofenóis/uso terapêutico , Aminofenóis/farmacologia , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Benzodioxóis/uso terapêutico , Benzodioxóis/farmacologia , Agonistas dos Canais de Cloreto/uso terapêutico , Agonistas dos Canais de Cloreto/farmacologia , Fibrose Cística/genética , Fibrose Cística/tratamento farmacológico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Modelos Animais de Doenças , Combinação de Medicamentos , Mutação , Quinolonas/farmacologia , Quinolonas/uso terapêutico
6.
Mol Ther Methods Clin Dev ; 32(2): 101244, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38638546

RESUMO

The dosing interval for effective recombinant adeno-associated virus (rAAV)-mediated gene therapy of cystic fibrosis lung disease remains unknown. Here, we assessed the durability of rAAV2.5T-fCFTRΔR-mediated transgene expression and neutralizing antibody (NAb) responses in lungs of adult wild-type ferrets. Within the first 3 months following rAAV2.5T-fCFTRΔR delivery to the lung, CFTRΔR transgene expression declined ∼5.6-fold and then remained stable to 5 months at ∼26% the level of endogenous CFTR. rAAV NAbs in the plasma and bronchoalveolar lavage fluid (BALF) peaked at 21 days, coinciding with peak ELISpot T cell responses to AAV capsid peptides, after which both responses declined and remained stable at 4-5 months post dosing. Administration of reporter vector rAAV2.5T-gLuc (gaussia luciferase) at 5 months following rAAV2.5T-fCFTRΔR dosing gave rise to similar levels of gLuc expression in the BALF as observed in age-matched reporter-only controls, demonstrating that residual BALF NAbs were functionally insignificant. Notably, the second vector administration led to a 2.6-fold greater ELISpot T cell response and ∼2.3-fold decline in fCFTRΔR mRNA and vector genomes derived from the initial rAAV2.5T-fCFTRΔR administration, suggesting selective destruction of transduced cells from the first vector dose. These findings provide insights into humoral and cellular immune response to rAAV that may be useful for optimizing gene therapy to the cystic fibrosis lung.

7.
Foods ; 13(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38672908

RESUMO

To investigate the gelation process of direct ultra-high-temperature (UHT) milk, a pilot-scale steam infusion heat treatment was used to process milk samples over a wide temperature of 142-157 °C for 0.116-6 s, followed by storage at 4 °C, 25 °C, and 37 °C. The results of the physicochemical properties of milk showed that the particle sizes and plasmin activities of all milk samples increased during storage at 25 °C, but age gelation only occurred in three treated samples, 147 °C/6 s, 142 °C/6 s, and 142 °C/3 s, which all had lower plasmin activities. Furthermore, the properties of formed gels were further compared and analyzed by the measures of structure and intermolecular interaction. The results showed that the gel formed in the 147 °C/6 s-treated milk with a higher C* value had a denser network structure and higher gel strength, while the 142 °C/6 s-treated milk had the highest porosity. Furthermore, disulfide bonds were the largest contributor to the gel structure, and there were significant differences in disulfide bonds, hydrophobic interaction forces, hydrogen bonds, and electrostatic force among the gels. Our results showed that the occurrence of gel was not related to the thermal load, and the different direct UHT treatments produced different age gels in the milk.

8.
J Dairy Sci ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38554824

RESUMO

Ultra-instantaneous UHT (UI-UHT, > 155°C, < 0.1 s) treated milk exhibits higher retention of active protein than regular UHT milk. However, UI-UHT products demonstrate increased susceptibility to destabilization during storage. This study aimed at monitoring the destabilizing process of UI-UHT milk across different storage temperatures and uncovering its potential mechanisms. Compared with regular UHT treatment, ultra-instantaneous treatment markedly accelerated the milk's destabilization process. Aged gel formation occurred after 45 d of storage at 25°C, while creaming and sedimentation were observed after 15 d at 37°C. To elucidate the instability mechanism, measurements of plasmin activity, protein hydrolysis levels, and proteomics of the aged gel were conducted. In UI-UHT milk, plasmin activity, and protein hydrolysis levels significantly increased during storage. Excessive protein hydrolysis at 37°C resulted in sedimentation, while moderate hydrolysis and an increase in protein particle size at 25°C resulted in aged gel formation. Proteomics analysis results indicated that the aged gel from UI-UHT milk contained intact caseins, major whey proteins, and their derived peptides. Furthermore, specific whey proteins including albumin, lactotransferrin, enterotoxin-binding glycoprotein PP20K, and MFGM proteins were identified in the gel. Additionally, MFGM proteins in UI-UHT milk experienced considerable hydrolysis during storage, contributing to fat instability. This study lays a theoretical foundation for optimizing UI-UHT milk storage conditions to enhance the quality of liquid milk products.

9.
ACS Nano ; 18(6): 4871-4885, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38290527

RESUMO

Diabetic wounds exhibit delayed and incomplete healing, usually due to vascular and nerve damage. Dysregulation of cellular Ca2+ homeostasis has recently been shown to be closely related to insulin resistance and type 2 diabetes mellitus. However, the involvement of this dysregulation in diabetic wound complications remains unknown. In this study, we found calcium dysregulation in patients with diabetic ulcers via tissue protein profiling. High glucose and glucometabolic toxicant stimulation considerably impaired the function of TRPC6, a pore subunit of transient receptor potential channels mediating Ca2+ influx, and mitochondria, which regulate calcium cycling and metabolism. Furthermore, we found that mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEVs) could play a dual role in restoring the function of TRPC6 and mitochondria by delivering transcription factor SP2 and deubiquitinating enzyme USP9, respectively. MSC-sEVs could transfer SP2 that activated TRPC6 expression by binding to its specific promoter regions (-1519 to -1725 bp), thus recovering Ca2+ influx and downstream pathways. MSC-sEVs also promoted mitophagy to restore mitochondrial function by transporting USP9 that stabilized the expression of Parkin, a major player in mitophagy, thereby guaranteeing Ca2+ efflux and avoidance of Ca2+ overload. Targeting the regulation of calcium homeostasis provides a perspective for understanding diabetic wound healing, and the corresponding design of MSC-sEVs could be a potential therapeutic strategy.


Assuntos
Diabetes Mellitus Tipo 2 , Vesículas Extracelulares , Células-Tronco Mesenquimais , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Canal de Cátion TRPC6/metabolismo , Cálcio/metabolismo , Cicatrização/fisiologia , Células-Tronco Mesenquimais/metabolismo , Vesículas Extracelulares/metabolismo , Mitocôndrias/metabolismo
10.
Oral Dis ; 30(2): 292-306, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36704830

RESUMO

OBJECTIVES: In order to predict the patients' prognosis with tongue squamous cell carcinoma (SCC), this study set out to develop a clinically useful and trustworthy prognostic nomogram. SUBJECTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program was used to compile clinical information on patients with tongue SCC between 2010 and 2015. The likelihood of Cancer-Specific Survival (CSS) and Overall Survival (OS) for specific patients was predicted using a prognostic nomogram created with the help of the RStudio software. The nomogram's predictive ability was evaluated using the consistency index (C-index) and decision curve analysis, and the nomogram was calibrated for 1-, 2-, 3-, 5-, and 10-year CSS and OS. RESULTS: Patients numbering 6453were enrolled in this study. The primary cohort (3895) and validation cohort (2558) were each randomly assigned. Sex, age, tumor-node-metastasis (TNM) stage, surgery, chemotherapy, and radiation were significant risk factors for OS, whereas age, TNM stage, surgery, chemotherapy, and radiotherapy were significant risk factors for CSS. Additionally, C-index and calibration curves indicated that the prognostic nomogram prediction and the actual observation in both cohorts would be very coherent. CONCLUSIONS: The predictive nomogram created in this study can offer patients with tongue SCC customized treatment and survival risk assessment.


Assuntos
Carcinoma de Células Escamosas , Neoplasias da Língua , Humanos , Prognóstico , Nomogramas , Carcinoma de Células Escamosas/terapia , Neoplasias da Língua/terapia , Língua
11.
Materials (Basel) ; 16(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38138763

RESUMO

Superhydrophobic coatings have increasingly become the focal point of research due to their distinctive properties like water resistance, wear resistance, and acid-base resilience. In pursuit of maximizing their efficiency, research has primarily revolved around refining the fabrication process and the composition of emulsion/nanoparticle coatings. We innovatively devised a superhydrophobic coating by employing a spraying technique. This involved integrating a γ-Methacryloyloxypropyltrimethoxysilane (KH570)-modified ZrO2/SiO2/silicone-modified acrylic emulsion. A comprehensive evaluation of this coating was undertaken using analytical instruments such as Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and confocal laser scanning microscopy (CLSM). The coating demonstrated exceptional performance across a range of tests, including wear, immersion, and anti-icing cleaning, showcasing notable wear resistance, sodium chloride corrosion resistance, self-cleaning efficiency, and thermal stability. In particular, one coating exhibited super-hydrophobic properties, with a high contact angle of 158.5 degrees and an impressively low rolling angle of 1.85 degrees. This remarkable combination of properties is attributed to the judicious selection of components, which significantly reinforced the mechanical strength of the coating. These enhancements make it highly suitable for industrial applications where self-cleaning, anti-icing, and anti-contamination capabilities are critical.

13.
J Nanobiotechnology ; 21(1): 451, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012570

RESUMO

Spinal cord injury (SCI) is a traumatic condition of the central nervous system that causes paralysis of the limbs. Micro electric fields (EF) have been implicated in a novel therapeutic approach for nerve injury repair and regeneration, but the effects of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles that are induced by micro electric fields (EF-sEVs) stimulation on SCI remain unknown. The aim of the present study was to investigate whether EF-sEVs have therapeutic effects a rat model of SCI. EF-sEVs and normally conditioned human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (CON-sEVs) were collected and injected intralesionally into SCI model rats to evaluate the therapeutic effects. We detect the expression of candidate long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA-MALAT1) in EF-sEVs and CON-sEVs. The targets and downstream effectors of lncRNA-MALAT1 were investigated using luciferase reporter assays. Using both in vivo and in vitro experiments, we demonstrated that EF-sEVs increased autophagy and decreased apoptosis after SCI, which promoted the recovery of motor function. We further confirmed that the neuroprotective effects of EF-sEVs in vitro and in vivo correlated with the presence of encapsulated lncRNA-MALAT1 in sEVs. lncRNA-MALAT1 targeted miR-22-3p via sponging, reducing miR-22-3p's suppressive effects on its target, SIRT1, and this translated into AMPK phosphorylation and increased levels of the antiapoptotic protein Bcl-2. Collectively, the present study identified that the lncRNA-MALAT1 in EF-sEVs plays a neuroprotective role via the miRNA-22-3p/SIRT1/AMPK axis and offers a fresh perspective and a potential therapeutic approach using sEVs to improve SCI.


Assuntos
Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Traumatismos da Medula Espinal , Ratos , Humanos , Animais , RNA Longo não Codificante/metabolismo , Proteínas Quinases Ativadas por AMP , Sirtuína 1/genética , Sirtuína 1/metabolismo , Apoptose , Traumatismos da Medula Espinal/metabolismo , MicroRNAs/metabolismo , Autofagia
14.
J Cancer Surviv ; 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37971555

RESUMO

PURPOSE: Lifelong self-management plays a critical role in the prevention and management of lymphedema among breast cancer survivors. However, adherence to lymphedema self-management behaviors has remained suboptimal. Hence, we adopted a theory-informed method to elucidate the facilitators and barriers of lymphedema self-management for breast cancer survivors. METHODS: In-depth semi-structured interviews were conducted between August and October 2022 in the lymphedema nursing clinic of a tertiary cancer hospital. The maximum variation sampling technique was used to ensure a diverse sample. The ITHBC (Integrated Theory of Health Behavior Change) framework was used to inform the interview outline and data analysis. Interview transcripts were coded line-by-line and mapped to domains in accordance with the ITHBC, using both deductive and inductive content analysis. RESULTS: A total of 16 participants were interviewed (aged 35 to 67). Twenty-three themes (12 facilitators and 11 barriers) were mapped onto the three domains (knowledge and belief, social facilitation, and self-regulation skill and ability) of ITHBC as facilitators and barriers to lymphedema self-management. Three additional themes including limited treatment resources for lymphedema, inconvenience of lymphedema management, boredom and tedium of lymphedema self-management were categorized under the domain of other barriers. CONCLUSIONS: Incorporating these findings into the ITHBC framework allows for a more systematic selection of theory-based strategies that may improve the design of effective lymphedema self-management interventions for breast cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Elucidating impact factors, especially facilitators and barriers, for lymphedema self-management adherence is essential for developing effective intervention programs to enhance breast cancer survivors' lymphedema self-management behaviors.

15.
Heliyon ; 9(10): e20426, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37842615

RESUMO

Background: The 2022 Beijing Winter Olympics is a representative large-scale sporting event, which not only promotes the development of the national and regional economy, society, and culture but also increases the demand of residents for winter sports, thus helping achieve the grand goal of "encouraging 300 million people to participate in winter sports." This research explores the influence of the Beijing Winter Olympics on residents' demand for winter sports in the Beijing-Tianjin-Hebei and Yangtze River Delta urban agglomerations in China. Methods: Applying big data mining techniques, the Baidu Index of Winter Olympics-related terms are used to measure residents' interest in the Beijing Winter Olympics, and the ratio of the Baidu Index of five winter sports (ice skating, ice hockey, curling, luge, and skiing) to the number of internet searches is used to capture residents' demand for winter sports. Moreover, we explore the spatial-temporal pattern of the interest in the Winter Olympics and the demand for winter sports and construct an econometric model to test the driving effect of the Winter Olympics empirically. Results: The results show that 1) since 2011, interest in Winter Olympics has been on the rise, and the interest of residents in Beijing-Tianjin-Hebei has been higher than that of the Yangtze River Delta; 2) the demand for skating and skiing, which are two popular winter sports, shows a declining geographical concentration, indicating that the popularity of these two sports is on the increase; 3) the demand for winter sports in the peripheral cities in Beijing-Tianjin-Hebei shows a trend of specialization, while Beijing, Tianjin, and some cities in the Yangtze River Delta present a trend of diversification; and 4) the interest in the Beijing Winter Olympics influences the demand for winter sports positively. Conclusion: This study shows that the increase in interest in the Beijing Winter Olympics boosts residents' demand for winter sports, which implies that hosting Winter Olympics successfully drives winter sports participation in China.

16.
Child Adolesc Psychiatry Ment Health ; 17(1): 113, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794411

RESUMO

BACKGROUND: The psychological impact of the COVID-19 pandemic has been understudied among vulnerable populations. This study aimed to examine the immediate and longer-term changes in the mental health of children with parent-child separation experiences during the COVID-19 pandemic, and identify potential buffering opportunities for mental health. METHODS: This longitudinal cohort study used data from 723 rural Chinese children who provided data before (Oct. 2019) the COVID-19 pandemic and during the following 2 years. Changes in the probability of depressive symptoms, anxiety symptoms, non-suicide self-injurious (NSSI), suicidal ideation, suicide plan, and suicide attempt were tested across four waves using generalized estimating models (GEE). RESULTS: Compared with children who never experienced parent-child separation, children persistently separated from parents since birth experienced greater deterioration in all mental health in the 2-year follow-up (average change: depressive symptoms: ß = 0.59, 95% CI [0.26, 0.93]; anxiety symptoms: ß = 0.45, 95% CI [0.10, 0.81]; NSSI: ß = 0.66, 95% CI [0.31, 1.01]; suicide ideation: ß = 0.67, 95% CI [0.38, 0.96]; suicide plan: ß = 0.77, 95% CI [0.38, 1.15]; suicide attempt: ß = 1.12, 95% CI [0.63, 1.62]). However, children with childhood separation from their parents but reunited with them during the transition to adolescence showed similar even lower changes to counterparts who never experienced parent-child separation (all ps > 0.05). CONCLUSION: These results indicating improvements in supportiveness of the caregiving environment during the transition to adolescence may provide the opportunity to buffer the adverse impact of COVID-19 on mental health. Translating such knowledge to inform intervention and prevention strategies for youths exposed to adversity is a critical goal for the field.

17.
Toxicol Appl Pharmacol ; 477: 116697, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37734572

RESUMO

Arsenic exposure is associated with an increased risk of many cancers, and epigenetic mechanisms play a crucial role in arsenic-mediated carcinogenesis. Our previous studies have shown that arsenic exposure induces polyadenylation of H3.1 mRNA and inhibits the deposition of H3.3 at critical gene regulatory elements. However, the precise underling mechanisms are not yet understood. To characterize the factors governing arsenic-induced inhibition of H3.3 assembly through H3.1 mRNA polyadenylation, we utilized mass spectrometry to identify the proteins, especially histone chaperones, with reduced binding affinity to H3.3 under conditions of arsenic exposure and polyadenylated H3.1 mRNA overexpression. Our findings reveal that the interaction between H3.3 and the histone chaperon protein MCM2 is diminished by both polyadenylated H3.1 mRNA overexpression and arsenic treatment in human lung epithelial BEAS-2B cells. The increased binding of MCM2 to H3.1, resulting from elevated H3.1 protein levels, appears to contribute to the reduced availability of MCM2 for H3.3. To further investigate the role of MCM2 in H3.3 deposition during arsenic exposure and H3.1 mRNA polyadenylation, we overexpressed MCM2 in BEAS-2B cells overexpressing polyadenylated H3.1 or exposed to arsenic. Our results demonstrate that MCM2 overexpression attenuates H3.3 depletion at several genomic loci, suggesting its involvement in the arsenic-induced displacement of H3.3 mediated by H3.1 mRNA polyadenylation. These findings suggest that changes in the association between histone chaperone MCM2 and H3.3 due to polyadenylation of H3.1 mRNA may play a pivotal role in arsenic-induced carcinogenesis.


Assuntos
Arsênio , Humanos , Arsênio/toxicidade , Arsênio/química , Chaperonas de Histonas/genética , Carcinogênese , Genômica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Componente 2 do Complexo de Manutenção de Minicromossomo/química , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo
18.
Front Mol Biosci ; 10: 1183530, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37593129

RESUMO

Objective: This study investigated to probe ferroptosis-related diagnostic biomarkers and underlying molecular mechanisms in Diabetic nephropathy (DN). Methods: GSE30122 and GSE1009 from GEO database were used as training and verification sets, respectively, to screen differentially expressed ferroptosis-related genes (FRGs). These genes were further analyzed using GO, KEGG, and GSEA methods, and screened with PPI, LASSO, and SVM-RFE to identify ferroptosis-related diagnostic biomarkers for DN. A diagnostic model was established using the Glm function and verified with ROC curve. The relationship between these biomarkers and immune cell was analyzed, and qRT-PCR and Western blot were used to detect the expression of these biomarkers in kidney tissues and identify the effect of TP53 on DN development. Results: Fifty one differentially expressed FRGs were enriched in bioprocesses such as p53 signaling pathway, oxidative stress and chemical stress response, and mTOR signaling pathway. TP53, RB1, NF2, RRM2, PRDX1, and CDC25A were identified as ferroptosis-related diagnostic biomarkers for DN. TP53 showed the most differential expression. ROC analysis showed that AUC values of TP53, RB1, NF2, RRM2, PRDX1, and CDC25A were 0.751, 0.705, 0.725, 0.882, 0.691, and 0.675, respectively. The AUC value of DN diagnosis model was 0.939 in training set and 1.000 in verification set. qRT-PCR results confirmed significant differences in these six biomarkers between DN and normal kidney tissue (p < 0.05), and correlation analysis showed that five biomarkers were significantly correlated with infiltrating immune cells (p < 0.05). Furthermore, western blots showed that TP53 promotes apoptosis through PI3K-AKT signaling in DN. Conclusion: TP53, RB1, NF2, RRM2, PRDX1, and CDC25A have potential as diagnostic biomarkers for DN. The diagnostic model containing the above six biomarkers performs well in the diagnosis of DN. Five of the six biomarkers are strongly associated with several infiltrating immune cells. TP53 may play an essential role in the development of DN.

19.
Environ Sci Technol ; 57(39): 14589-14601, 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37585923

RESUMO

Sea ice (including overlying snow) is a dynamic interface between the atmosphere and the ocean, influencing the mercury (Hg) cycling in polar oceans. However, a large-scale and process-based model for the Hg cycle in the sea ice environment is lacking, hampering our understanding of regional Hg budget and critical processes. Here, we develop a comprehensive model for the Hg cycle at the ocean-sea ice-atmosphere interface with constraints from observational polar cryospheric data. We find that seasonal patterns of average total Hg (THg) in snow are governed by snow thermodynamics and deposition, peaking in springtime (Arctic: 5.9 ng/L; Antarctic: 5.3 ng/L) and minimizing during ice formation (Arctic: 1.0 ng/L, Antarctic: 0.5 ng/L). Arctic and Antarctic sea ice exhibited THg concentration peaks in summer (0.25 ng/L) and spring (0.28 ng/L), respectively, governed by different snow Hg transmission pathways. Antarctic snow-ice formation facilitates Hg transfer to sea ice during spring, while in the Arctic, snow Hg is primarily moved through snowmelt. Overall, first-year sea ice acts as a buffer, receiving atmospheric Hg during ice growth and releasing it to the ocean in summer, influencing polar atmospheric and seawater Hg concentrations. Our model can assess climate change effects on polar Hg cycles and evaluate the Minamata Convention's effectiveness for Arctic populations.

20.
J Clin Nurs ; 32(19-20): 7330-7345, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37491890

RESUMO

AIMS AND OBJECTIVES: The purpose of this empirical study was to explore the current status and associated factors of lymphedema self-management behaviours among Chinese breast cancer survivors. BACKGROUND: Breast cancer-related lymphedema is a lifetime concern for survivors and is currently incurable. Lifetime lymphedema self-management takes a significant role in preventing development and progression of lymphedema. Understanding influencing factors of lymphedema self-management behaviours can help to develop targeted intervention programs. DESIGN: A multicentre cross-sectional study. METHODS: From December 2021 to April 2022, a convenience sample of 586 participants were recruited at four tertiary hospitals in four cities in China. Self-reported questionnaires were used to measure socio-demographic characteristics, disease-and treatment-related characteristics, lymphedema self-management behaviours, lymphedema knowledge, illness perception, self-efficacy, self-regulation and social support. Descriptive analysis, bivariate analysis and hierarchical multiple regression were conducted. This study was registered at Chinese Clinical Trial Registry (ChiCTR2200057084), and was reported followed the STROBE checklist. RESULTS: Breast cancer survivors reported moderate level of lymphedema self-management behaviours. Promotion of lymph reflux management was ranked the least performed self-management behaviours, while the affected limb protection management ranked the most. 36.2% of self-management behaviours was explained by exercise regularly, level of attention on lymphedema prevention, unclear about the tumour stage (vs. stage I), knowledge, self-efficacy, emotional illness representation and social support. CONCLUSIONS: Lymphedema self-management behaviours of breast cancer survivors was insufficient. Performance of lymphedema self-management varied with different socio-demographic characteristics, along with different levels of knowledge, self-efficacy, perception and social support. All these identified predictors should be reckoned in assessment and intervention of lymphedema self-management behaviours. RELEVANCE TO CLINICAL PRACTICE: This study addressed that breast cancer survivors' lymphedema self-management behaviours should be promoted. Focusing on identified predictors, further lymphedema surveillance, knowledge education or social facilitation programs are recommended to enhance their self-management performance and adherence.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Linfedema , Autogestão , Humanos , Feminino , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Neoplasias da Mama/psicologia , Estudos Transversais , Linfedema/prevenção & controle , Sobreviventes/psicologia
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