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2.
Front Nutr ; 11: 1431962, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39104758

RESUMO

Background: Globally, diet low in milk is the third greatest risk factor for colorectal cancer (CRC). However, there has been a lack of detailed worldwide analysis of the burden and trends of CRC attributable to diet low in milk. Objective: We aim to assess the spatiotemporal trends of CRC-related mortality and disability-adjusted life-years (DALYs) attributable to diet low in milk at the global, regional, and national levels from 1990 to 2019. Methods: Data of mortality, DALYs, age-standardized mortality rate (ASMR), and age-standardized DALY rate (ASDR) of CRC attributable to diet low in milk were extracted from the Global Burden of Disease (GBD) 2019 study. The burden of CRC attributable to diet low in milk was estimated using the ASMR and ASDR, while accounting for sex, age, country, and socio-demographic index (SDI). From 1990 to 2019, the estimated annual percentage change (EAPC) was calculated to clarify the temporal trends in the ASMR and ASDR attributable to diet low in milk. Results: In 2019, there were 166,456 (95% UI = 107,221-226,027) deaths and 3,799,297 (95% UI = 2,457,768-5,124,453) DALYs attributable to diet low in milk, accounting for 15.3 and 15.6% of CRC-related deaths and DALYs in 2019. CRC-related deaths and DALYs attributed to diet low in milk increased by 130.5 and 115.4%, from 1990 to 2019. The burden of CRC attributable to diet low in milk varied notably among regions and nations. High-middle SDI regions had the highest ASDR and ASMR of CRC linked to diet low in milk, while there was a slight downward trend high SDI regions. Among geographical regions, East Asia had the highest number of CRC-related deaths and DALYs attributable to diet low in milk. Notably, the burden of CRC was highest in males and the elderly. With coefficients of -0.36 and -0.36, the EAPC in ASMR and ASDR was significantly inversely correlated with the Human Development Index in 2019. Conclusion: Globally, the number of CRC deaths attributable to diet low in milk has continued to increase over the last 30 years. Therefore, government and authorities should conduct education campaigns to encourage individuals to increase daily milk intake.

3.
Chem Biodivers ; : e202401081, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39126188

RESUMO

The aberrant activation of NLRP3 inflammasomes is intricately linked to various inflammatory diseases. In this study, we present the discovery and optimization of a series of NLRP3 inflammasome inhibitors based on the pterostilbene skeleton. All compounds underwent screening to evaluate their inhibitory effects on LPS/Nigericin-induced IL-1ß secretion and anti-cellular pyroptosis. Most compounds exhibit good biological activity and cellular safety, with compound D20 showing the most prominent activity. Preliminary mechanism studies suggest that compound D20 may affect the assembly of NLRP3 inflammasomes by targeting the NLRP3 protein, thereby inhibiting the activation of NLRP3 inflammasomes. The in vivo anti-inflammatory activity demonstrated significant therapeutic effect of compound D20 on DSS-induced acute colitis model in mice. This work has important reference significance for the development of drugs targeting NLRP3 inflammasomes.

4.
RSC Med Chem ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39157854

RESUMO

It is of great significance to design and synthesize novel structural inhibitors with good antitumor activity. In this study, based on rational design, a total of 42 7-azaindole derivatives as novel CDK8 inhibitors were designed and synthesized. All compounds were screened with antitumor activity and compound 6 (1-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)phenyl)-3-(m-tolyl)urea) exhibited the best activity, especially in acute myeloid leukemia (GI50 MV4-11 = 1.97 ± 1.24 µM). This compound also exhibited excellent inhibitory activity against CDK8 (IC50 = 51.3 ± 4.6 nM). Further mechanism studies shown that it could inhibit STAT5 phosphorylation and induce cell cycle arrest in the G1 phase, leading to apoptosis in acute myeloid leukemia cells. In addition, acute toxicity at a dose of 1000 mg kg-1 indicated the low toxicity of this compound.

5.
Int Immunopharmacol ; 141: 112883, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39153305

RESUMO

Ectodermal mesenchymal stem cells-derived conditioned medium (EMSCs-CM) has been reported to protect against ulcerative colitis (UC) in mice, but its underlying mechanism in alleviating UC need to be further elucidated. Here, it is reported that EMSCs-CM could attenuate pro-inflammatory response of LPS-induced IEC-6 cells and regulate the polarization of macrophages towards anti-inflammatory type in vitro. Furthermore, PLGA microspheres prepared by the double emulsion method were constructed for oral delivery of EMSCs-CM (EMSCs-CM-PLGA), which are beneficial for colon-targeted adhesion of EMSCs-CM to the damaged colon mucosa. The results showed that orally-administered of EMSCs-CM-PLGA microspheres reduced inflammatory cells infiltration and maintained the intestinal mucosal barrier. Further investigation found that EMSCs-CM-PLGA microspheres treatment gradually inhibited the activation of NF-κB pathway to regulate M1/M2 polarization balance in colon tissue macrophages, thereby alleviating DSS-induced UC. These results of this study will provide a theoretical basis for clinical application of EMSCs-CM in UC repair.

6.
Public Health Nurs ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39054588

RESUMO

BACKGROUND: Unsafe sex is recognized as an important risk factor for cervical cancer (CC). Understanding the global disease burden of CC attributable to unsafe sex can assist policymakers in allocating healthcare resources. METHODS: Data were obtained from the 2019 global burden of disease database (GBD). We examined global, regional, and national levels of CC mortality, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) caused by unsafe sex. ASRs were evaluated using estimated annual percentage changes (EAPCs). RESULTS: Attributable to unsafe sex, there were 280,479 CC-related deaths in 2019 and 8,955,013 CC-related DALYs. In the period 1990-2019, the global ASRs of CC due to unsafe sex decreased around the world; for age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR), the EAPCs were -0.93 and -0.95. The highest ASMRs and ASDRs were found in central sub-Saharan Africa and the lowest in Australasia. CONCLUSION: In the past few decades, the ASMR and ASDR of CC caused by unsafe sexual practices have decreased over time, with significant variations observed among different countries and regions. Increased focus is needed on spreading awareness about sexual health and promoting CC prevention and screening, particularly in low- and middle-income nations.

7.
Sci Total Environ ; 948: 174855, 2024 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-39034010

RESUMO

Nitrification is highly crucial for both anammox systems and the global nitrogen cycle. The discovery of complete ammonia oxidation (comammox) challenges the inherent concept of nitrification as a two-step process. Its wide distribution, adaptability to low substrate environments, low sludge production, and low greenhouse gas emissions may make it a promising new nitrogen removal treatment process. Meanwhile, anammox technology is considered the most suitable process for future wastewater treatment. The diverse metabolic capabilities and similar ecological niches of comammox bacteria and anammox bacteria are expected to achieve synergistic nitrogen removal within a single system. However, previous studies have overlooked the existence of comammox, and it is necessary to re-evaluate the conclusions drawn. This paper outlined the ecophysiological characteristics of comammox bacteria and summarized the environmental factors affecting their growth. Furthermore, it focused on the enrichment, regulatory strategies, and nitrogen removal mechanisms of comammox and anammox, with a comparative analysis of hydroxylamine, a particular intermediate product. Overall, this is the first critical overview of the conclusions drawn from the last few years of research on comammox-anammox, highlighting possible next steps for research.


Assuntos
Amônia , Nitrificação , Nitrogênio , Oxirredução , Eliminação de Resíduos Líquidos , Nitrogênio/metabolismo , Eliminação de Resíduos Líquidos/métodos , Amônia/metabolismo , Bactérias/metabolismo , Águas Residuárias , Reatores Biológicos/microbiologia , Anaerobiose
8.
PeerJ Comput Sci ; 10: e2120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983221

RESUMO

Server load levels affect the performance of cloud task execution, which is rooted in the impact of server performance on cloud task execution. Traditional cloud task scheduling methods usually only consider server load without fully considering the server's real-time load-performance mapping relationship, resulting in the inability to evaluate the server's real-time processing capability accurately. This deficiency directly affects the efficiency, performance, and user experience of cloud task scheduling. Firstly, we construct a performance platform model to monitor server real-time load and performance status information in response to the above problems. In addition, we propose a new deep reinforcement learning task scheduling method based on server real-time performance (SRP-DRL). This method introduces a real-time performance-aware strategy and adds status information about the real-time impact of task load on server performance on top of considering server load. It enhances the perception capability of the deep reinforcement learning (DRL) model in cloud scheduling environments and improves the server's load-balancing ability under latency constraints. Experimental results indicate that the SRP-DRL method has better overall performance regarding task average response time, success rate, and server average load variance compared to Random, Round-Robin, Earliest Idle Time First (EITF), and Best Fit (BEST-FIT) task scheduling methods. In particular, the SRP-DRL is highly effective in reducing server average load variance when numerous tasks arrive within a unit of time, ultimately optimizing the performance of the cloud system.

9.
Angew Chem Int Ed Engl ; : e202410666, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007416

RESUMO

Near-infrared region (NIR; 650-1700 nm) dyes offer many advantages over traditional dyes with absorption and emission in the visible region. However, developing new NIR dyes, especially organic dyes with long wavelengths, small molecular weight, and excellent stability and biocompatibility, is still quite challenging. Herein, we present a general method to enhance the absorption and emission wavelengths of traditional fluorophores by simply appending a charge separation structure, dihydropyridopyrazine. These novel NIR dyes not only exhibited greatly redshifted wavelengths compared to their parent dyes, but also displayed a small molecular weight increase together with retained stability and biocompatibility. Specifically, dye NIR-OX, a dihydropyridopyra-zine derivative of oxazine with a molecular mass of 386.2 Da, exhibited an absorption at 822 nm and an emission extending to 1200 nm, making it one of the smallest molecular-weight NIR-II emitting dyes. Thanks to its rapid metabolism and long wave-length, NIR-OX enabled high-contrast bioimaging and assessment of cholestatic liver injury in vivo and also facilitated the evalua-tion of the efficacy of liver protection medicines against cholestatic liver injury.

10.
Environ Sci Ecotechnol ; 21: 100440, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38993655

RESUMO

Anaerobic digestion (AD) plays a significant role in renewable energy recovery. Upgrading AD from thermophilic (50-57 °C) to mesophilic (30-38 °C) conditions to enhance process stability and reduce energy input remains challenging due to the high sensitivity of thermophilic microbiomes to temperature fluctuations. Here we compare the effects of two decreasing-temperature modes from 55 to 35 °C on cell viability, microbial dynamics, and interspecies interactions. A sharp transition (ST) is a one-step transition by 20 °C d-1, while a mild transition (MT) is a stepwise transition by 1 °C d-1. We find a greater decrease in methane production with ST (88.8%) compared to MT (38.9%) during the transition period. ST mode overproduced reactive oxygen species by 1.6-fold, increased membrane permeability by 2.2-fold, and downregulated microbial energy metabolism by 25.1%, leading to increased apoptosis of anaerobes by 1.9-fold and release of intracellular substances by 2.9-fold, further constraining methanogenesis. The higher (1.6 vs. 1.1 copies per gyrA) metabolic activity of acetate-dependent methanogenesis implied more efficient methane production in a steady mesophilic, MT-mediated system. Metagenomic binning and network analyses indicated that ST induced dysbiosis in keystone species and greatly enhanced microbial functional redundancy, causing loss of microbial syntrophic interactions and redundant metabolic pathways. In contrast, the greater microbial interconnections (average degrees 44.9 vs. 22.1) in MT at a steady mesophilic state suggested that MT could better maintain necessary system functionality and stability through microbial syntrophy or specialized pathways. Adopting MT to transform thermophilic digesters into mesophilic digesters is feasible and could potentially enhance the further optimization and broader application of practical anaerobic engineering.

11.
J Thorac Dis ; 16(5): 2906-2917, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38883678

RESUMO

Background: The efficacy of high-flow nasal cannula (HFNC) in patients extubated after lung resection surgery remains inconclusive. Our objective was to execute a meticulous systematic meta-analysis to accurately assess the advantages of HFNC compared to conventional oxygen therapy (COT) for patients extubated after lung resection surgery, by examining postoperative hypoxemia and other patient-focused outcomes. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science and Scopus to identify randomized controlled trials (RCTs) from inception to July 2023. We employed the revised Cochrane risk of bias (RoB) tool (2.0) to evaluate the RoB of the included studies, and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method to ascertain the certainty of the pooled effect estimates. The primary outcome was the incidence of postoperative hypoxemia. Results: Five RCTs (n=564) were included in the ultimate analysis. Utilizing HFNC rather than COT did not reduce the risk of postoperative hypoxemia [relative risk (RR), 0.67; 95% confidence interval (CI): 0.30-1.49; low certainty]. Compared to COT, HFNC may significantly enhance oxygenation index within first 12 hours after extubation in patients with lung resection. There were no significant differences in reintubation rate (RR, 0.25; 95% CI: 0.04-1.54; high certainty), escalation of respiratory support (RR, 0.35; 95% CI: 0.11-1.08; high certainty), change in partial pressure of carbon dioxide (PaCO2) within first 24 hours after extubation, hospital length of stay [mean difference (MD), -0.19; 95% CI: -0.44 to 0.06; moderate certainty], and intensive care unit (ICU) length of stay (MD, 0.02; 95% CI: -0.16 to 0.19; high certainty). Conclusions: Our meta-analysis suggests that preemptive use of HFNC, instead of COT, in extubated patients following lung resection surgery may not significantly impact postoperative hypoxemia incidence, reintubation rate, escalation of respiratory support, postoperative PaCO2 difference, hospital and ICU length of stay. However, HFNC may significantly enhance the oxygenation index within the first 12 hours post-extubation following lung resection surgery. To verify the effect of HFNC on this population, additional large-scale, multicenter studies are essential.

12.
Environ Technol ; : 1-7, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38875359

RESUMO

Using oil recovery wastewater as the target material, the degradation of organic matter in oilfield wastewater was studied in an anodic oxidation system using Ti/Ru-Ir oxide-coated anode and 0.7mMNa2SO4 as the electrolyte. The TOC of the wastewater was 210 mg/L at the beginning of the electrolysis in the electrolysis system, and it decreased from 210 to 93.6 mg/L after 50 min of electrolysis. Under the action of this system, sulfate was oxidized to persulfate, and the apparent concentration of persulfate was 15.02 mM, oxidation and degradation of organic matter in wastewater by the action of newly generated persulfate.. Afterwards, NaOH and Fe2(SO4)3 were added to the electrolyzed wastewater, and the TOC in the wastewater was further reduced to 25.1 mg/L due to the coagulation effect of the newly generated Fe(OH)3 precipitate. The TOC removal rate of the wastewater treated by this process reached 88.0%, which meets the discharge requirements. At the same time, the derived persulfate oxidized Fe(OH)3 to generate a green substance, which was identified as Na2FeO3 by IR, UV, and XRD analyses. Na2FeO3 served as a highly effective water-purifying agent, demonstrating superior performance when compared to FeO42-. The method reported in this study not only provides a strategy for waste resource recycling but also offers the potential for mass production of ferrate (IV).

13.
J Hazard Mater ; 475: 134886, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878435

RESUMO

Minimization of antibiotic resistance genes (ARGs) and potential pathogenic antibiotic-resistant bacteria (PARB) during anaerobic digestion (AD) is significantly impacted by temperature. However, knowledge on how ARGs and PARB respond to temperature transition from thermophilic to mesophilic is limited. Here, we combined metagenomic-based with culture-based approaches and revealed the risks of antimicrobial resistance and pathogenicity during transition from 55 °C to 35 °C for AD, with strategies of sharp (ST, one-step by 20 °C/d) and mild (MT, step-wise by 1 °C/d). Results indicated a lower decrease in methane production with MT (by 38.9%) than ST (by 88.8%). Phenotypic assays characterized a significant propagation of multi-resistant lactose-fermenting Enterobacteriaceae and indicator pathogens after both transitions, especially via ST. Further genomic evidence indicated a significant increase of ARGs (29.4-fold), virulence factor genes (1.8-fold) and PARB (65.3-fold) after ST, while slight enrichment via MT. Bacterial succession and enhanced horizontal transfer mediated by mobile genetic elements promoted ARG propagation in AD during transition, which was synchronously exacerbated through horizontal transfer mechanisms mediated by cellular physiological responses (oxidative stress, membrane permeability, bacterial conjugation and transformation) and co-selection mechanisms of biomethanation metabolic functions (acidogenesis and acetogenesis). This study reveals temperature-dependent resistome and pathogenicity development in AD, facilitating microbial risk control.


Assuntos
Farmacorresistência Bacteriana , Anaerobiose , Farmacorresistência Bacteriana/genética , Temperatura , Metano/metabolismo , Bactérias/genética , Bactérias/patogenicidade , Bactérias/metabolismo , Bactérias/efeitos dos fármacos , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Fatores de Virulência/genética , Transferência Genética Horizontal , Enterobacteriaceae/genética , Enterobacteriaceae/patogenicidade , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/metabolismo , Genes Bacterianos
14.
Int Immunopharmacol ; 137: 112532, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38908087

RESUMO

Sepsis-associated acute lung injury (ALI) poses a significant threat, characterized by inflammation and oxidative damage. Effective drugs targeting these aspects with reliable drug delivery systems are vital for ALI management. This study aimed to evaluate the influence of algal polysaccharides (APs) with aerosolized drug delivery in ALI mice and clarify the underlying mechanism. To induce the sepsis-associated acute lung injury (ALI) model, mice were administered intraperitoneal injections of 10 mg/kg LPS for 48 h in vivo. ALI mice received APs via atomization to arrive at different sites within the lungs. Lung tissue samples and bronchoalveolar lavage fluid (BALF) were collected to access lung injury parameters. Concurrently, western blotting, H&E staining, and immunofluorescence (IF) were applied to investigate the specific impact of APs on ALI. The results showed that APs protect lung tissue against ALI by inhibiting inflammation and mitigating oxidative stress-induced damage. This study highlights promising avenues for ALI intervention using natural compounds with anti-inflammatory and antioxidant properties.


Assuntos
Lesão Pulmonar Aguda , Anti-Inflamatórios , Pulmão , Estresse Oxidativo , Polissacarídeos , Animais , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/uso terapêutico , Polissacarídeos/farmacologia , Polissacarídeos/administração & dosagem , Administração por Inalação , Camundongos , Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/administração & dosagem , Masculino , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Pneumonia/tratamento farmacológico , Modelos Animais de Doenças , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/química , Lipopolissacarídeos , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Camundongos Endogâmicos C57BL , Sepse/tratamento farmacológico , Aerossóis , Inflamação/tratamento farmacológico , Humanos
15.
Neuropsychologia ; 200: 108910, 2024 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-38777117

RESUMO

Attention control is the common element underlying different executive functions. The backward Masking Majority Function Task (MFT-M) requires intensive attention control, and represents a diverse situation where attentional resources need to be allocated dynamically and flexibly to reduce uncertainty. Aiming to train attention control using MFT-M and examine the training transfer effects in various executive functions, we recruited healthy young adults (n = 84) and then equally randomized them into two groups trained with either MFT-M or a sham program for seven consecutive days. Cognitive evaluations were conducted before and after the training, and the electroencephalograph (EEG) signals were recorded for the revised Attention Network Test (ANT-R), N-back, and Task-switching (TS) tasks. Compared to the control group, the training group performed better on the congruent condition of Flanker and the double-congruency condition of Flanker and Location in the ANT-R task, and on the learning trials in the verbal memory test. The training group also showed a larger P2 amplitude decrease and P3 amplitude increase in the 2-back task and a larger P3 amplitude increase in the TS task's repeat condition than the control group, indicating improved neural efficiency in two tasks' attentional processes. Introversion moderated the transfer effects of training, as indicated by the significant group*introversion interactions on the post-training 1-back efficiency and TS switching cost. Our results suggested that attention control training with the MFT-M showed a broad transfer scope, and the transfer effect was influenced by the form of training task. Introversion facilitated the transfer to working memory and hindered the transfer to flexibility.


Assuntos
Atenção , Eletroencefalografia , Função Executiva , Transferência de Experiência , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Atenção/fisiologia , Cognição/fisiologia , Potenciais Evocados/fisiologia , Função Executiva/fisiologia , Testes Neuropsicológicos , Transferência de Experiência/fisiologia
16.
Hum Vaccin Immunother ; 20(1): 2343192, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38745409

RESUMO

To summarize the distribution of types of human papillomavirus (HPV) associated with HPV-related diseases and investigate the potential causes of high prevalence of HPV 52 and 58 by summarizing the prevalence of lineages, sub-lineages, and mutations among Chinese women. We searched PubMed, EMBASE, CNKI, and WanFang from January, 2012 to June, 2023 to identify all the eligible studies. We excluded patients who had received HPV vaccinations. Data were summarized in tables and cloud/rain maps. A total of 102 studies reporting HPV distribution and 15 studies reporting HPV52/HPV58 variants were extracted. Among Chinese women, the top five prevalent HPV types associated with cervical cancer (CC) were HPV16, 18, 58, 52, and 33. In patients with vaginal cancers and precancerous lesions, the most common HPV types were 16 and 52 followed by 58. For women with condyloma acuminatum (CA), the most common HPV types were 11 and 6. In Chinese women with HPV infection, lineage B was the most prominently identified for HPV52, and lineage A was the most common for HPV58. In addition to HPV types 16, which is prevalent worldwide, our findings revealed the unique high prevalence of HPV 52/58 among Chinese women with HPV-related diseases. HPV 52 variants were predominantly biased toward lineage B and sub-lineage B2, and HPV 58 variants were strongly biased toward lineage A and sub-lineage A1. Further investigations on the association between the high prevalent lineage and sub-lineage in HPV 52/58 and the risk of cancer risk are needed. Our findings underscore the importance of vaccination with the nine-valent HPV vaccine in China.


Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , China/epidemiologia , Prevalência , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/epidemiologia , Papillomaviridae/genética , Papillomaviridae/classificação , Genótipo , Neoplasias Vaginais/virologia , Neoplasias Vaginais/epidemiologia , Condiloma Acuminado/virologia , Condiloma Acuminado/epidemiologia
17.
Sci Rep ; 14(1): 10642, 2024 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724565

RESUMO

Colorectal cancer (CRC) often necessitates cetuximab (an EGFR-targeting monoclonal antibody) for treatment. Despite its clinical utility, the specific operative mechanism of cetuximab remains elusive. This research investigated the influence of PLCB3, a potential CRC oncogene, on cetuximab treatment. We extracted differentially expressed genes from the GSE140973, the overlapping genes combined with 151 Wnt/ß-Catenin signaling pathway-related genes were identified. Then, we conducted bioinformatics analysis to pinpoint the hub gene. Subsequently, we investigated the clinical expression characteristics of this hub gene, through cell experimental, scrutinized the impact of cetuximab and PLCB3 on CRC cellular progression. The study identified 26 overlapping genes. High expression of PLCB3, correlated with poorer prognosis. PLCB3 emerged as a significant oncogene associated with patient prognosis. In vitro tests revealed that cetuximab exerted a cytotoxic effect on CRC cells, with PLCB3 knockdown inhibiting CRC cell progression. Furthermore, cetuximab treatment led to a reduction in both ß-catenin and PLCB3 expression, while simultaneously augmenting E-cadherin expression. These findings revealed PLCB3 promoted cetuximab inhibition on Wnt/ß-catenin signaling. Finally, simultaneous application of cetuximab with a Wnt activator (IM12) and PLCB3 demonstrated inhibited CRC proliferation, migration, and invasion. The study emphasized the pivotal role of PLCB3 in CRC and its potential to enhance the efficacy of cetuximab treatment. Furthermore, cetuximab suppressed Wnt/ß-catenin pathway to modulate PLCB3 expression, thus inhibiting colorectal cancer progression. This study offered fresh perspectives on cetuximab mechanism in CRC.


Assuntos
Cetuximab , Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Wnt , beta Catenina , Humanos , Antineoplásicos Imunológicos/farmacologia , beta Catenina/metabolismo , beta Catenina/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cetuximab/farmacologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Prognóstico , Via de Sinalização Wnt/efeitos dos fármacos
19.
Infect Dis Model ; 9(3): 816-827, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38725432

RESUMO

Background: Influenza is an acute respiratory infectious disease with a significant global disease burden. Additionally, the coronavirus disease 2019 pandemic and its related non-pharmaceutical interventions (NPIs) have introduced uncertainty to the spread of influenza. However, comparative studies on the performance of innovative models and approaches used for influenza prediction are limited. Therefore, this study aimed to predict the trend of influenza-like illness (ILI) in settings with diverse climate characteristics in China based on sentinel surveillance data using three approaches and evaluate and compare their predictive performance. Methods: The generalized additive model (GAM), deep learning hybrid model based on Gate Recurrent Unit (GRU), and autoregressive moving average-generalized autoregressive conditional heteroscedasticity (ARMA-GARCH) model were established to predict the trends of ILI 1-, 2-, 3-, and 4-week-ahead in Beijing, Tianjin, Shanxi, Hubei, Chongqing, Guangdong, Hainan, and the Hong Kong Special Administrative Region in China, based on sentinel surveillance data from 2011 to 2019. Three relevant metrics, namely, Mean Absolute Percentage Error (MAPE), Root Mean Squared Error (RMSE), and R squared, were calculated to evaluate and compare the goodness of fit and robustness of the three models. Results: Considering the MAPE, RMSE, and R squared values, the ARMA-GARCH model performed best, while the GRU-based deep learning hybrid model exhibited moderate performance and GAM made predictions with the least accuracy in the eight settings in China. Additionally, the models' predictive performance declined as the weeks ahead increased. Furthermore, blocked cross-validation indicated that all models were robust to changes in data and had low risks of overfitting. Conclusions: Our study suggested that the ARMA-GARCH model exhibited the best accuracy in predicting ILI trends in China compared to the GAM and GRU-based deep learning hybrid model. Therefore, in the future, the ARMA-GARCH model may be used to predict ILI trends in public health practice across diverse climatic zones, thereby contributing to influenza control and prevention efforts.

20.
World J Clin Cases ; 12(12): 2092-2098, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38680263

RESUMO

BACKGROUND: This study aimed to explore the relationship between gene mutations and early embryonic development arrest and to provide more possibilities for the diagnosis and treatment of repeated implantation failure. CASE SUMMARY: Here, we collected and described the clinical data of a patient with early embryonic development stagnation after repeated in vitro fertilization attempts for primary infertility at the Department Reproductive Center of Zaozhuang Maternal and Child Healthcare Hospital. We also detected the whole-exon gene of the patient's spouse and parents, and conducted bioinformatics analysis to determine the pathogenesis of the gene. CONCLUSION: A novel mutant of the TUBB8 gene [c.602G>T(p.C201F)] was identified, and this mutant provided new data on the genotype-phenotype relationships of related diseases.

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