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1.
ACS Appl Mater Interfaces ; 16(25): 32078-32086, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38865735

RESUMO

The traditional recognition of extracellular matrix (ECM) at tissue sections relies on the time-consuming immunofluorescence that could not meet the demand of rapid diagnosis. Herein, we introduce a thickness-resolved electrochemiluminescence (ECL) microscopy to image thin-layer ECM at tissue sections for fast histopathological analysis. The unique surface-confined ECL mechanism enables to unveil the diversity and complexity of multiple tissue structures with varying thicknesses. Notably, the short lifetimes and the limited diffusion of electrogenerated coreactant radicals combined with their chemical reactivity result in a 2-fold increase in ECL intensity on ECM structures compared to the remaining tissue, enabling ECM visualization without specific labeling. The further quantitation of the ECM localization within tissue sections furnishes crucial insights into tumor progression and, more importantly, differentiates carcinoma and paracancerous tissues from patients in less than 30 min. Moreover, the reported electrochemistry-based microscopy is a dynamic approach allowing to investigate the transport, tortuosity, and trafficking properties through the tissues. This thickness-resolved recognition strategy not only opens new avenues for imaging complex samples but also holds promise for expediting tissue pathologic diagnosis, offering a more automated protocol with enhanced quantitative data compared to current intraoperative pathology methods.


Assuntos
Técnicas Eletroquímicas , Matriz Extracelular , Neoplasias , Humanos , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Técnicas Eletroquímicas/métodos , Neoplasias/diagnóstico , Neoplasias/patologia , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Medições Luminescentes/métodos , Microscopia/métodos
2.
J Hazard Mater ; 474: 134736, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38815394

RESUMO

We established an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneously analyzing the metabolites of bisphenols and phthalates in urine to identify the associations between these exposure levels and prostate cancer (PCa) based on a case-control study. After purifying urine samples with SPE, 18 metabolites were separated on a C18 column, and MS detection was performed. The UPLC-MS/MS method has been proven effective at evaluating bisphenol and phthalate exposure (0.020-0.20 µg/L of the limits of detection, 71.8 %∼119.4 % of recoveries, 0.4 %∼8.2 % of precision). Logistic regression explored the association between exposure level and PCa in 187 PCa cases and 151 controls. The detection rates of bisphenol A (BPA) and most phthalate metabolites were 100 % ranging from 0.06-46.74 and 0.12-899.92 µg/g creatinine, respectively, while the detection rates of other bisphenols and mono-benzyl phthalate (MBzP) are low, ranging from 0 % to 21.85 %. Correlation analysis of the metabolite levels indicated that the exposure sources of BPA, di-ethyl phthalate (DEP), and di(2-ethylhexyl) phthalate (DEHP) were different, and that the exposure sources of di-n-butyl phthalate (DnBP) and di-isobutyl phthalate (DiBP) may differ between two groups. Logistic regression analysis revealed that BPA (OR<0.45 vs ≥1.43 =10.02) and DEHP exposure (OR<21.75 vs ≥45.42 =48.26) increased the risk of PCa.


Assuntos
Compostos Benzidrílicos , Exposição Ambiental , Fenóis , Ácidos Ftálicos , Neoplasias da Próstata , Neoplasias da Próstata/urina , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/epidemiologia , Masculino , Fenóis/urina , Fenóis/análise , Humanos , Ácidos Ftálicos/urina , Ácidos Ftálicos/análise , Compostos Benzidrílicos/urina , Estudos de Casos e Controles , Pessoa de Meia-Idade , Idoso , Exposição Ambiental/análise , Espectrometria de Massas em Tandem , Poluentes Ambientais/urina , Poluentes Ambientais/análise , Cromatografia Líquida de Alta Pressão
3.
Psychiatry Investig ; 21(4): 361-370, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38695043

RESUMO

OBJECTIVE: The purpose of this study was to identify the associations of chronic physical disease between patients with severe mental illness (SMI) and the general population of South Korea. METHODS: This study was conducted with National Health Insurance Corporation data from 2014 to 2019. A total of 848,058 people were diagnosed with SMI in this period, and the same number of controls were established by matching by sex and age. A descriptive analysis was conducted on the sociodemographic characteristics of patients with SMI. Conditional logistic regression analysis was performed to identify the associations between comorbid physical disease in patients with SMI and those of the general population. SAS Enterprise Guide 7.1 (SAS Inc, Cary, NC, USA) were used to perform all statistical tests. RESULTS: The analysis revealed significant differences in medical insurance, income level, and Charlson Comorbidity Index weighted by chronic physical disease, between patients with SMI and the general population. Conditional logistic regression analysis between the two groups also revealed significant differences in eight chronic physical diseases except hypertensive disease. CONCLUSION: This study confirmed the vulnerability of patients with SMI to chronic physical diseases and we were able to identify chronic physical disease that were highly related to patients with SMI.

4.
Sci Bull (Beijing) ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38760248

RESUMO

Mechanical loading is required for bone homeostasis, but the underlying mechanism is still unclear. Our previous studies revealed that the mechanical protein polycystin-1 (PC1, encoded by Pkd1) is critical for bone formation. However, the role of PC1 in bone resorption is unknown. Here, we found that PC1 directly regulates osteoclastogenesis and bone resorption. The conditional deletion of Pkd1 in the osteoclast lineage resulted in a reduced number of osteoclasts, decreased bone resorption, and increased bone mass. A cohort study of 32,500 patients further revealed that autosomal dominant polycystic kidney disease, which is mainly caused by loss-of-function mutation of the PKD1 gene, is associated with a lower risk of hip fracture than those with other chronic kidney diseases. Moreover, mice with osteoclast-specific knockout of Pkd1 showed complete resistance to unloading-induced bone loss. A mechanistic study revealed that PC1 facilitated TAZ nuclear translocation via the C-terminal tail-TAZ complex and that conditional deletion of Taz in the osteoclast lineage resulted in reduced osteoclastogenesis and increased bone mass. Pharmacological regulation of the PC1-TAZ axis alleviated unloading- and estrogen deficiency- induced bone loss. Thus, the PC1-TAZ axis may be a potential therapeutic target for osteoclast-related osteoporosis.

5.
Front Med (Lausanne) ; 11: 1380369, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638932

RESUMO

This case report documents the first instance of Penicillin-Susceptible Methicillin-Resistant Staphylococcus aureus (PS-MRSA) in a Chinese psychiatric hospital. The strain was isolated from a patient with Alzheimer's disease who had a lower respiratory tract infection. Clinical and laboratory analyses, including mass spectrometry, antibiotic susceptibility testing, and whole-genome sequencing, confirmed the PS-MRSA strain. In this case, we systematically introduce the clinical symptoms, laboratory findings, and treatment responses associated with this PS-MRSA strain. This discovery offers a new perspective on our understanding of resistance mechanisms and expands our considerations for existing antibiotic treatments. It may fill a gap in the classification of MRSA strains, enhance the spectrum of MRSA resistance, and complete the therapeutic strategies for MRSA.

6.
Medicine (Baltimore) ; 103(16): e37763, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640273

RESUMO

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors, and stages III and IV are frequently diagnosed. In recent years, immunotherapy has achieved remarkable results in recurrent/metastatic NPC, and many studies related to immunotherapy for NPC have been published. However, to date, no relevant bibliometric studies have been published. The trends and research focus on NPC immunotherapy are analyzed in this study through bibliometric analysis, which is conducive to better understanding the status quo and future trends of immunotherapy for NPC. The Web of Science Core Collection was used to collect literature on NPC immunotherapy. These publications were analyzed using bibliometric methods from the aspects of country/region, institution, author (co-cited author), journal (co-cited journal), references, and keywords to determine the research focus and trends in the field. A total of 510 English studies were published between January 1, 2000 and September 1, 2023. The number of articles published increased rapidly in 2016. China ranked first in the number of publications (n = 254), followed by the United States (n = 127). Sun Yat-sen University had the largest number of publications (n = 74). In terms of authors, Comoli P is the most cited author among the co-cited authors. The journal publishing the largest number of studies on NPC immunotherapy is Frontiers in Oncology (impact factor (2022) = 4.7). Five of the top 10 highly cited publications came from China. Keyword analysis reveals that infiltrating lymphocytes, PD-L1, and the tumor microenvironment are recent research focuses on nasopharyngeal cancer immunotherapy. Immunotherapy research for nasopharyngeal cancer is a recent trend. Nasopharyngeal cancer immunotherapy research has mainly focused on immune checkpoint inhibitors and the tumor microenvironment. Notably, China has made significant contributions to this field.


Assuntos
Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/terapia , Carcinoma Nasofaríngeo/terapia , Imunoterapia , Bibliometria , China , Microambiente Tumoral
7.
Sci Rep ; 14(1): 9427, 2024 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658591

RESUMO

Lower-grade gliomas (LGGs) exhibit highly variable clinical behaviors, while classic histology characteristics cannot accurately reflect the authentic biological behaviors, clinical outcomes, and prognosis of LGGs. In this study, we carried out analyses of whole exome sequencing, RNA sequencing and DNA methylation in primary vs. recurrent LGG samples, and also combined the multi-omics data to construct a prognostic prediction model. TCGA-LGG dataset was searched for LGG samples. 523 samples were used for whole exome sequencing analysis, 532 for transcriptional analysis, and 529 for DNA methylation analysis. LASSO regression was used to screen genes with significant association with LGG survival from the frequently mutated genes, differentially expressed genes, and differentially methylated genes, whereby a prediction model for prognosis of LGG was further constructed and validated. The most frequently mutated diver genes in LGGs were IDH1 (77%), TP53 (48%), ATRX (37%), etc. Top significantly up-regulated genes were C6orf15, DAO, MEOX2, etc., and top significantly down-regulated genes were DMBX1, GPR50, HMX2, etc. 2077 genes were more and 299 were less methylated in recurrent vs. primary LGG samples. Thirty-nine genes from the above analysis were included to establish a prediction model of survival, which showed that the high-score group had a very significantly shorter survival than the low-score group in both training and testing sets. ROC analysis showed that AUC was 0.817 for the training set and 0.819 for the testing set. This study will be beneficial to accurately predict the survival of LGGs to identify patients with poor prognosis to take specific treatment as early, which will help improve the treatment outcomes and prognosis of LGG.


Assuntos
Neoplasias Encefálicas , Metilação de DNA , Glioma , Humanos , Glioma/genética , Glioma/patologia , Glioma/mortalidade , Prognóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Mutação , Masculino , Biomarcadores Tumorais/genética , Sequenciamento do Exoma , Gradação de Tumores , Perfilação da Expressão Gênica , Proteína Nuclear Ligada ao X/genética , Pessoa de Meia-Idade , Isocitrato Desidrogenase/genética , Multiômica
8.
J Cancer Res Clin Oncol ; 150(4): 180, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587528

RESUMO

BACKGROUND: To evaluate the clinical efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer in the real world. METHODS: The retrospective analysis was conducted on the clinical records of 402 patients with advanced gastric cancer who were admitted to the Nanjing Drum Tower Hospital between December 2017 and April 2022 and who had received immunotherapy. Observation target: drug use, treatment, adverse reaction type and grade, objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). RESULTS: By retrospectively analyzing the data of patients with advanced gastric cancer treated with ICIs previously admitted to our medical center, we found some clinical characteristic factors associated with the occurrence of irAEs as well as the efficacy and prognosis: the presence or absence of hypertension, whether or not to receive targeted therapies can predict the occurrence of immune-related adverse events (irAEs), and the more the presence of irAEs, the better the prognosis. These can help clinicians in clinical drug selection. CONCLUSIONS: The results of this paper show that the occurrence of irAEs is associated with patients' OS. irAEs occurrence can prolong patients' OS. irAEs occurrence may serve as a surrogate marker for ICIs.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias Gástricas , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Resultado do Tratamento , Intervalo Livre de Progressão
9.
Chem Biodivers ; 21(6): e202400511, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38538539

RESUMO

Two undescribed germacrane-type sesquiterpenoids, salcasins A (1) and B (2), together with three known compounds (3-5) were isolated and identified from the whole plant of Salvia cavaleriei var. simplicifolia Stib. The structures of the undescribed compounds were elucidated on the basis of spectroscopic methods, such as HR-ESI-MS, 1D and 2D NMR data. The relative configurations of 1 and 2 were established by analyzing their NOESY spectra as well as by 13C NMR calculations with DP4+ probability analyses. The absolute configurations of 1 and 2 were determined by comparing experimental and calculated ECD spectra. Furthermore, the in vivo anti-Alzheimer's disease activities of 1-5 were evaluated using Caenorhabditis elegans AD pathological model. Among all isolated compounds, salcasin A (1) significantly delayed AD-like symptoms of worm paralysis, which may be a potential anti-AD candidate agent.


Assuntos
Doença de Alzheimer , Caenorhabditis elegans , Salvia , Sesquiterpenos de Germacrano , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Salvia/química , Caenorhabditis elegans/efeitos dos fármacos , Sesquiterpenos de Germacrano/farmacologia , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Estrutura Molecular , Conformação Molecular , Modelos Animais de Doenças
10.
Toxicol Res ; 40(2): 247-258, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38525130

RESUMO

ATB1651 gel is an antifungal drug candidate that enhances antifungal activity through substitution of several aryl rings, alkyl chains, and methyl groups. To ensure safety of use of ATB1651 gel, assessment of its potentially toxic side effects is necessary. In this study, we examined the repeated-dose toxicity of ATB1651 gel to Yucatan minipigs (Sus scrofa) in accordance with the Good Laboratory Practice guidelines. Five doses of ATB1651 gel (0%, 0.2%, 0.5%, 1.0%, 3.0%) were administered dermally to the left and right flanks of 38 minipigs daily for 4 weeks. Mortality, clinical symptoms, dermal scores, body weights, and physiological, biochemical, pathological, and toxicokinetic analyses were performed after the treatment period. No systemic toxicological damage was observed in either male or female minipigs regardless of dose; however, dermal application of ATB1651 gel caused some skin alterations at the application sites. Specifically, erythema and eschar formation, edema, and scabs or raise spots were observed at the application site(s) in males in the 3.0% ATB1651 gel treatment group and in females at ATB1651 gel concentrations ≥ 1.0%, with dermal scores ranging from grade 1 to 2. Additionally, histopathological assay indicated infiltration of different types of inflammatory cells and the presence of pustule/crust at the application site(s) in both males and females at ATB1651 gel concentrations ≥ 0.5%. However, these changes were reversible after a 2-week recovery period and were considered a local irritation effect of ATB1651 gel. The no-observed-adverse-effect level of ATB1651 gel was 3.0% with regard to topical and systemic toxicity in both male and female minipigs. Collectively, our results imply that ATB1651 gel is a safe candidate for clinical development as an antifungal drug with a wide therapeutic window.

11.
World Neurosurg ; 184: 202-212, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38316176

RESUMO

OBJECTIVE: To comprehensively compare the safety and efficacy of endoscopic surgery (ES) and stereotactic aspiration (SA) in patients with spontaneous intracerebral hemorrhage (sICH). METHODS: We searched Web of Science, PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to July 31, 2023. Studies comparing ES and SA for sICH treatment were also included. Outcome measures included primary outcomes (mortality and good functional outcome [GFO]) and secondary outcomes (evacuation rate, residual hematoma, perihematomal edema (PHE), operation time, volume of intraoperative blood loss, hospital stay duration, intensive care unit stay duration, hospital cost, complications, and reoperation). Subgroup analyses assessed the influence of age, hematoma volume, Glasgow Coma Scale score, and time to surgery on the outcomes. RESULTS: Nine studies (1 randomized controlled trial and 8 observational studies) with 2105 patients (705 and 1400 in the ES and SA groups, respectively) were included in this meta-analysis. The final analysis indicated that compared with SA, ES was associated with enhanced GFO and a higher evacuation rate 1 day post-surgery along with reduced mortality and residual hematoma. Conversely, ES did not confer benefits in terms of perihematomal edema, operation time, intraoperative blood loss volume, or hospital stay duration compared with SA. Subgroup analysis highlighted the significant influences of age and hematoma volume on mortality, whereas hematoma volume and Glasgow Coma Scale score affected GFO. CONCLUSIONS: ES is a safe and effective approach for sICH treatment, leading to improved patient prognosis and quality of life compared to SA.


Assuntos
Perda Sanguínea Cirúrgica , Qualidade de Vida , Humanos , Resultado do Tratamento , Hemorragia Cerebral/cirurgia , Hemorragia Cerebral/complicações , Hematoma/etiologia , Edema , Estudos Retrospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Observacionais como Assunto
12.
Gland Surg ; 13(1): 19-31, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38323228

RESUMO

Background: The enhanced recovery after surgery (ERAS) protocols have been consistently associated with improved patient experience and surgical outcomes. Despite the release of ERAS Society guidelines specific to gynecologic oncology, the adoption of ERAS in gynecology on global level has been disappointingly low and some centers have shown minimal improvement in clinical outcomes after adopting ERAS. The aim of this study is to describe the development and early experience of ERAS protocols in gynecologic surgery at an urban academic tertiary medical center. Methods: This was an observational prospective cohort study. The target patient population included those with low comorbidities who were scheduled to undergo various types of gynecologic surgeries for both benign and malignant diseases between October 2020 and February 2021. Two attending surgeons implemented the protocols for their patients (ERAS cohort) while three attending surgeons maintained the conventional perioperative care for their patients (non-ERAS cohort). Baseline characteristics, surgical outcomes and patients' answers to a 12-question survey were compared. A case-matched comparative analysis was also performed between the ERAS cohort and the historical non-ERAS cohort (those who received the same types of surgical procedures from the two ERAS attending surgeons prior to the implementation of the protocols). Results: A total of 244 patients were evaluated (122 in the ERAS cohort vs. 122 in the non-ERAS cohort). The number of vials of opioid analgesia used during the first two postoperative days was significantly lower whereas the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen was more frequent in the ERAS cohort group. The patients in the ERAS group reported less postoperative pain, feelings of hunger and thirst, and greater amount of exercise postoperatively. These benefits of the ERAS cohort were more pronounced in the patients who underwent laparotomic surgeries than those who underwent laparoscopic surgeries. The case-matched comparative analysis also showed similar results. The length of hospital stay did not differ between those who underwent the ERAS protocols and those who did not. Conclusions: The results of the study demonstrated the safety, clinical feasibility and benefits of the ERAS protocols for patients undergoing gynecologic surgeries for both benign and malignant indications.

13.
Heliyon ; 10(3): e25045, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38317961

RESUMO

Inhalation of polyhexamethylene guanidine phosphate (PHMG) can cause pulmonary fibrosis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are enzymes that produce reactive oxygen species, which may be involved in tissue damage in various lung diseases. To investigate whether the Nox2 isoform of Nox is involved in the progression of PHMG-induced lung damage, we studied the contribution of Nox2 in PHMG-induced lung injury in Nox2-deficient mice. We treated wild-type (WT) and Nox2 knockout mice with a single intratracheal instillation of 1.1 mg/kg PHMG and sacrificed them after 14 days. We analyzed lung histopathology and the number of total and differential cells in the bronchoalveolar lavage fluid. In addition, the expressions of cytokines, chemokines, and profibrogenic genes were analyzed in the lung tissues. Based on our results, Nox2-deficient mice showed less PHMG-induced pulmonary damage than WT mice, as indicated by parameters such as body weight, lung weight, total cell count, cytokine and chemokine levels, fibrogenic mediator expression, and histopathological findings. These findings suggest that Nox2 may have the potential to contribute to PHMG-induced lung injury and serves as an essential signaling molecule in the development of PHMG-induced pulmonary fibrosis by regulating the expression of profibrogenic genes.

14.
Chem Commun (Camb) ; 60(11): 1464-1467, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38223951

RESUMO

Mercury sulfide (HgS) exerts extensive biological effects on neuronal function. To investigate the direct target of HgS in neuronal cells, we developed a biotin-tagged HgS probe (bio-HgS) and employed an affinity purification technique to capture its target proteins. Then, we identified S-phase kinase-associated protein 1 (Skp1) as a potential target of HgS. Unexpectedly, we discovered that HgS covalently binds to Skp1 through a "Cys62-HgS-Cys120" mode. Moreover, our findings revealed that HgS inhibits the ubiquitin-protease system through Skp1 to up-regulate SNAP-25 expression, thereby triggering synaptic vesicle exocytosis to regulate locomotion ability in C. elegans. Collectively, our findings may promote a comprehensive interpretation of the pharmacological mechanism of mercury sulfide on neuroprotective function.


Assuntos
Compostos de Mercúrio , Mercúrio , Animais , Mercúrio/metabolismo , Proteínas Quinases Associadas a Fase S , Caenorhabditis elegans/metabolismo , Neuroproteção , Sulfetos/metabolismo
15.
Bone Res ; 12(1): 6, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38267422

RESUMO

Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.


Assuntos
Calosidades , Fraturas Ósseas , Idoso , Humanos , Animais , Camundongos , Consolidação da Fratura , Senescência Celular , Envelhecimento , Macrófagos , Células-Tronco
16.
Environ Int ; 184: 108447, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38246039

RESUMO

INTRODUCTION: Although previous studies investigated the potential adverse effects of endocrine-disrupting chemicals (EDCs) on biological age acceleration and aging-related diseases, the mixed effect of multiple types of EDCs on biological age acceleration, including its potential underlying mechanism, remains unclear. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) were used to analyze biological age measures, including Klemera-Doubal method biological age (KDM-BA), phenotypic age, and homeostatic dysregulation (HD). Weight quantile sum (WQS) regression was performed to screen biological age-related EDCs (BA-EDCs) and assess the mixed effect of BA-EDCs on biological age acceleration and aging-related disease. Targets of BA-EDCs were obtained from three databases, while heart aging-related genes were obtained from the Aging Anno database. Protein-protein interaction (PPI) network and MCODE algorithm were applied to identify potential interactions between BA-EDC targets and heart aging-related genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to identify related pathways. RESULTS: This cross-sectional study included 1,439 participants. A decile increase in BA-EDCs co-exposure was associated with 0.31 years and 0.17 years of KDM-BA and phenotypic age acceleration, respectively. The mixed effect of BA-EDCs was associated with an increased prevalence of atherosclerotic cardiovascular disease (ASCVD). Vitamins C and E demonstrated a significant interaction effect on the association between BA-EDCs and KDM-BA acceleration. PPI network and functional enrichment analysis indicated that the AGE-RAGE signaling pathway in diabetic complications was significantly enriched. CONCLUSION: Our results showed that the co-exposure effect of BA-EDCs was associated with biological age acceleration and ASCVD, with the AGE-RAGE signaling pathway being the underlying mechanism. Vitamins C and E may also be an actionable target for preventing EDC-induced biological aging.


Assuntos
Disruptores Endócrinos , Humanos , Inquéritos Nutricionais , Disruptores Endócrinos/toxicidade , Estudos Transversais , Envelhecimento , Vitaminas
17.
Acta Pharmaceutica Sinica ; (12): 161-165, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005451

RESUMO

Based on the principle of molecular hybridization, fifteen compounds were designed and synthesized through the combination of aminothiazoloxime and phosphonate fragment. The results showed that these compounds had better inhibitory effects on the tested bacteria. In particular, the activities of compounds Ⅲf and Ⅲi against S. aureus, E. coli, methicillin-resistant S. aureus (MRSA) and fluoroquinolone-resistant E. coli (FREC) were the most significant, the minimal inhibitory concentration (MIC) of Ⅲf was 1, 8, 4, 16 μg·mL-1 respectively, and the MIC of Ⅲi was 4, 4, 16, 8 μg·mL-1 respectively, which were slightly lower than that of the control drug oxacillin, and their anti-E. coli, MRSA and FREC activities were superior to that of the control drug oxacillin. Their activities to S. aureus were close to that of oxacillin, and to E. coli, MRSA and FREC were superior to that of oxacillin, which is worthy of further study.

18.
Environ Toxicol ; 39(4): 2304-2315, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38148711

RESUMO

Cigarette smoke induces an inflammatory response in the lungs by recruiting inflammatory cells, leading to lung diseases such as lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Existing inhalation exposure methods for assessing the adverse effects of cigarette smoke require expensive equipment and are labor-intensive. Therefore, we attempted to develop a novel method to assess these adverse effects using intratracheal instillation (ITI) of whole cigarette smoke condensate (WCSC). The WCSC (0, 5, 10, or 20 mg/mL) was administered by ITI once daily for 6 or 12 days using an automatic video instillator. Repeated WCSC ITI increased the lung weight, and monocyte chemoattractant protein-1 (MCP-1), neutrophil, and lymphocyte levels within bronchoalveolar lavage fluid compared to the control. In the histopathological analysis of the lung tissue, a mild inflammatory response was observed in the 6 and 12 days 20 mg/mL WCSC exposure groups. The genome-wide RNA-seq expression patterns revealed that inflammatory and immune response-related genes, such as the chemokine signaling pathway, Th1/Th2 cell differentiation, and cytokine-cytokine receptor interaction, were employed following WCSC exposure. In addition, MCP-1 was time-dependent and increased in the 10 mg/mL exposure group compared to the control group. These results suggested that the WCSC might induce the potential pulmonary inflammatory response. Furthermore, we proposed that ITI may be a rapid and effective method of evaluating the adverse effects of WCSC within a short exposure period (less than 2 weeks), and it can be used to evaluate cigarette inhalation toxicity studies as an alternative method.


Assuntos
Fumar Cigarros , Pneumopatias , Doença Pulmonar Obstrutiva Crônica , Ratos , Animais , Pulmão , Doença Pulmonar Obstrutiva Crônica/metabolismo , Pneumopatias/patologia , Líquido da Lavagem Broncoalveolar
19.
World J Clin Cases ; 11(35): 8284-8290, 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38130614

RESUMO

BACKGROUND: Bronchiolitis is a common lower respiratory tract infection in infants and young children. Severe cases may be accompanied by obvious dyspnea and oxygen saturation decline. AIM: To summarize the clinical features, standard diagnosis, and treatment of bronchiolitis. METHODS: This is a retrospective analysis of 114 pediatric patients (74 males, 40 females) who were first diagnosed as having bronchioles at the Department of Pediatrics of Tongling Maternal and Child Health Hospital from January 2019 to December 2019. The clinical features, imaging features, treatment, and other clinical data were recorded and analyzed. RESULTS: The age of onset of the disease was mainly from 1 mo to 6 mo (75.4%), and the time to hospital visit was mostly from the 2nd day to the 4th day of the course of the disease (75.4%). Lung imaging examination showed increase in lung texture, fuzzy (93.8%). The main treatment was atomization therapy: Budesonide combined with terbutaline (45.6%) and budesonide combined with salbutamol (38.5%). The average hospitalization time was 7.1 ± 2.4 d, and the overall cure rate was 94.7%. In patients without bacterial infection, the use of antibiotics significantly prolonged the length of hospital stay (7.8 ± 2.5 d vs 5.7 ± 1.8 d) and improved the cure rate (98.3% vs 87.9%, P < 0.05). CONCLUSION: Infants with bronchiolitis are mainly male and tend to have a good prognosis. However, the unneeded use of antibiotics may prolong the length of hospital stay significantly, which imposes the burden both on the patients and hospital system.

20.
Molecules ; 28(22)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38005287

RESUMO

In order to investigate the flavour characteristics of aromatic, glutinous, and nonaromatic rice, gas chromatography-ion mobility spectrometry (GC-IMS) was used to analyse the differences in volatile organic compounds (VOCs) amongst different rice varieties. The results showed that 103 signal peaks were detected in these rice varieties, and 91 volatile flavour substances were identified. Amongst them, 28 aldehydes (28.89~31.17%), 24 alcohols (34.85~40.52%), 14 ketones (12.26~14.74%), 12 esters (2.30~4.15%), 5 acids (7.80~10.85%), 3 furans (0.30~0.68%), 3 terpenes (0.34~0.64%), and 2 species of ethers (0.80~1.78%) were detected. SIMCA14.1 was used to perform principal component analysis (PCA) and orthogonal partial least squares discriminant analysis, and some potential character markers (VIP > 1) were further screened out of the 91 flavour substances identified based on the variable important projections, including ethanol, 1-hexanol, hexanal, heptanal, nonanal, (E)-2-heptenal, octanal, trans-2-octenal, pentanal, acetone, 6-methyl-5-hepten-2-one, ethyl acetate, propyl acetate, acetic acid, and dimethyl sulphide. Based on the established fingerprint information, combined with principal component analysis and orthogonal partial least squares discriminant analysis, different rice varieties were also effectively classified, and the results of this study provide data references for the improvement in aromatic rice varieties.

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