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1.
Mar Life Sci Technol ; 6(2): 183-197, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38827131

RESUMO

Histone modification and nucleosome assembly play important roles in chromatin-related processes. Histone chaperones form different complexes and coordinate histone transportation and assembly. Various histone chaperone complexes have been identified in different organisms. The ciliate protozoa (ciliates) have various chromatin structures and different nuclear morphology. However, histone chaperone components and functions of different subunits remain unclear in ciliates. Tetrahymema thermophila contains a transcriptionally active macronucleus (MAC) and a transcriptionally inactive micronucleus (MIC) which exhibit multiple replication and various chromatin remodeling progresses during vegetative growth and sexual developmental stages. Here, we found histone chaperone RebL1 not only localized evenly in the transcriptionally active MAC but also dynamically changed in the MIC during vegetative growth and sexual developmental stages. REBL1 knockdown inhibited cellular proliferation. The macronuclear morphology became bigger in growing mutants. The abnormal macronuclear structure also occurred in the starvation stage. Furthermore, micronuclear meiosis was disturbed during sexual development, leading to a failure to generate new gametic nuclei. RebL1 potentially interacted with various factors involved in histone-modifying complexes and chromatin remodeling complexes in different developmental stages. REBL1 knockdown affected expression levels of the genes involved in chromatin organization and transcription. Taken together, RebL1 plays a vital role in maintaining macronuclear structure stability and gametogenesis in T. thermophila. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00219-z.

2.
Chem Biodivers ; : e202401093, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867371

RESUMO

Two previously undescribed coumarins (1-2) were isolated from the root of Notopterygium incisum. The structures of new findings were elucidated by analyses of spectral evidences in HRESIMS, NMR, as well as ICD. The absolute configurations were further confirmed by chemical calculations. 1-2 exhibits obviously anti-inflammatory activity by inhibiting the expression of inflammatory mediators (COX-2, iNOS), as well as reducing the release of NO and the accumulation of ROS in cells. Western blotting analysis revealed that 2 could inhibit the PI3K/AKT pathway by reducing the expression of p-PI3K and p-AKT.

3.
Tree Physiol ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861416

RESUMO

Heaping is an unavoidable process before olive milling, and its duration significantly affects the olive quality. However, there is limited research on the quality changes of olive fruits on a short-time scale. To gain a better understanding of the molecular mechanisms underlying postharvest deterioration of olives, this study piled olives at room temperature and extracted oil at 0 h, 8 h, 24 h, 48 h and 72 h to analyze oil quality parameters. GC/LC-MS techniques were employed to investigate variations in metabolite contents. Concurrently, the transcriptional profiles of olives during heaping were examined. As piling time progressed, quality indicators declined, and stored fruit were categorized into three groups based on their quality characters: '0 h' belongs to the first category, '8 h' and '24 h' to the second category, and '48 h' and '72 h' to the third category. Metabolite changes were consistent with the expression patterns of genes related to their synthesis pathways. Additionally, ethylene was identified as a crucial factor influencing fruit senescence. These findings establish a foundation for further research on olive deterioration after harvesting and offer insights for optimizing olive oil production.

4.
Nat Commun ; 15(1): 4755, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834568

RESUMO

Non-alcoholic steatohepatitis (NASH) is a severe type of the non-alcoholic fatty liver disease (NAFLD). NASH is a growing global health concern due to its increasing morbidity, lack of well-defined biomarkers and lack of clinically effective treatments. Using metabolomic analysis, the most significantly changed active lipid sphingosine d18:1 [So(d18:1)] is selected from NASH patients. So(d18:1) inhibits macrophage HIF-2α as a direct inhibitor and promotes the inflammatory factors secretion. Male macrophage-specific HIF-2α knockout and overexpression mice verified the protective effect of HIF-2α on NASH progression. Importantly, the HIF-2α stabilizer FG-4592 alleviates liver inflammation and fibrosis in NASH, which indicated that macrophage HIF-2α is a potential drug target for NASH treatment. Overall, this study confirms that So(d18:1) promotes NASH and clarifies that So(d18:1) inhibits the transcriptional activity of HIF-2α in liver macrophages by suppressing the interaction of HIF-2α with ARNT, suggesting that macrophage HIF-2α may be a potential target for the treatment of NASH.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Macrófagos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica , Esfingosina , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/genética , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Masculino , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Humanos , Camundongos , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Fígado/metabolismo , Fígado/patologia , Fígado/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Cirrose Hepática/genética , Modelos Animais de Doenças
5.
Nat Commun ; 15(1): 4792, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839760

RESUMO

Innate lymphoid cell precursors (ILCPs) develop into distinct subsets of innate lymphoid cells (ILCs) with specific functions. The epigenetic program underlying the differentiation of ILCPs into ILC subsets remains poorly understood. Here, we reveal the genome-wide distribution and dynamics of the DNA methylation and hydroxymethylation in ILC subsets and their respective precursors. Additionally, we find that the DNA hydroxymethyltransferase TET1 suppresses ILC1 but not ILC2 or ILC3 differentiation. TET1 deficiency promotes ILC1 differentiation by inhibiting TGF-ß signaling. Throughout ILCP differentiation at postnatal stage, gut microbiota contributes to the downregulation of TET1 level. Microbiota decreases the level of cholic acid in the gut, impairs TET1 expression and suppresses DNA hydroxymethylation, ultimately resulting in an expansion of ILC1s. In adult mice, TET1 suppresses the hyperactivation of ILC1s to maintain intestinal homeostasis. Our findings provide insights into the microbiota-mediated epigenetic programming of ILCs, which links microbiota-DNA methylation crosstalk to ILC differentiation.


Assuntos
Diferenciação Celular , Metilação de DNA , Proteínas de Ligação a DNA , Imunidade Inata , Linfócitos , Proteínas Proto-Oncogênicas , Animais , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Camundongos , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Linfócitos/metabolismo , Linfócitos/imunologia , Camundongos Endogâmicos C57BL , Microbioma Gastrointestinal , Epigênese Genética , Camundongos Knockout , Fator de Crescimento Transformador beta/metabolismo , Transdução de Sinais
6.
Cancer Imaging ; 24(1): 76, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886780

RESUMO

BACKGROUND: A standard surgical procedure for patients with small early-stage lung adenocarcinomas remains unknown. Hence, we aim in this study to assess the clinical utility of the consolidation-to-tumor ratio (CTR) when treating patients with small (2 cm) early stage lung cancers. METHODS: A retrospective cohort of 298 sublobar resection and 266 lobar resection recipients for early stage lung adenocarcinoma ≤ 2 cm was assembled from the First Affiliated Hospital of Chongqing Medical University between 2016 and 2019. To compare survival rates among the different groups, Kaplan-Meier curves were calculated, and the log-rank test was used. A multivariate Cox proportional hazard model was constructed utilizing variables that were significant in univariate analysis of survival. RESULTS: In the study, 564 patients were included, with 298 patients (52.8%) undergoing sublobar resection and 266 patients (47.2%) undergoing lobar resection. Regarding survival results, there was no significant difference in the 5-year overall survival (OS, P = 0.674) and 5-year recurrence-free survival (RFS, P = 0.253) between the two groups. Cox regression analyses showed that CTR ≥ 0.75(P < 0.001), age > 56 years (P = 0.007), and sublobar resection(P = 0.001) could predict worse survival. After examining survival results based on CTR categorization, we segmented the individuals into three categories: CTR<0.7, 0.7 ≤ CTR<1, and CTR = 1.The lobar resection groups had more favorable clinical outcomes than the sublobar resection groups in both the 0.7 ≤ CTR < 1(RFS: P < 0.001, OS: P = 0.001) and CTR = 1(RFS: P = 0.001, OS: P = 0.125). However, for patients with 0 ≤ CTR < 0.7, no difference in either RFS or OS was found between the lobar resection and sublobar resection groups, all of which had no positive events. Patients with a CTR between 0.7 and 1 who underwent lobar resection had similar 5-year RFS and OS rates compared to those with a CTR between 0 and 0.7 who underwent sublobar resection (100% vs. 100%). Nevertheless, a CTR of 1 following lobar resection resulted in notably reduced RFS and OS when compared to a CTR between 0.7 and 1 following lobar resection (P = 0.005 and P = 0.016, respectively). CONCLUSION: Lobar resection is associated with better long-term survival outcomes than sublobar resection for small lung adenocarcinomas ≤ 2 cm and CTR ≥ 0.7.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Pneumonectomia , Humanos , Masculino , Feminino , Estudos Retrospectivos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Idoso , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/mortalidade , Pneumonectomia/métodos , Taxa de Sobrevida , Prognóstico
7.
PLoS One ; 19(6): e0303692, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38875291

RESUMO

Electrical signaling plays a crucial role in the cellular response to tissue injury in wound healing and an external electric field (EF) may expedite the healing process. Here, we have developed a standalone, wearable, and programmable electronic device to administer a well-controlled exogenous EF, aiming to accelerate wound healing in an in vivo mouse model to provide pre-clinical evidence. We monitored the healing process by assessing the re-epithelization rate and the ratio of M1/M2 macrophage phenotypes through histology staining. Following three days of treatment, the M1/M2 macrophage ratio decreased by 30.6% and the re-epithelization in the EF-treated wounds trended towards a non-statically significant 24.2% increase compared to the control. These findings provide point towards the effectiveness of the device in shortening the inflammatory phase by promoting reparative macrophages over inflammatory macrophages, and in speeding up re-epithelialization. Our wearable device supports the rationale for the application of programmed EFs for wound management in vivo and provides an exciting basis for further development of our technology based on the modulation of macrophages and inflammation to better wound healing.


Assuntos
Modelos Animais de Doenças , Inflamação , Macrófagos , Cicatrização , Animais , Camundongos , Inflamação/terapia , Inflamação/patologia , Masculino , Dispositivos Eletrônicos Vestíveis
8.
Artigo em Inglês | MEDLINE | ID: mdl-38886916

RESUMO

This study aimed to understand nurses' perceptions of COVID-19-related policies and risks during the outbreak of COVID-19 in Hong Kong and to determine how their perceptions influenced their mental health status. A web-based online survey among Hong Kong nurses was conducted. The questionnaire included a self-designed 5-point Likert scale with 17 items to assess the nurses' perceptions of COVID-19-related policies and risks, as well as the Davidson Trauma Scale (DTS), the Perceived Stress Scale (PSS), the Patient Health Questionnaire-2 (PHQ-2) and the Generalised Anxiety Disorder scale (GAD) for measurement of posttraumatic stress disorder (PTSD), stress, depression and anxiety, respectively. Of 592 nurses enrolled, 30.6% had PTSD (DTS total score ≥40), and 80.4%, 19.9% and 16.4% had moderate-to-high levels of stress (PSS-10 score ≥14), depression (PHQ-2 score ≥3) and anxiety (GAD score ≥3), respectively. The top three concerned aspects were 'worried about themselves and friends to suffer this disease' (84.5%), 'insufficient number of isolation wards' (81.8%) and 'insufficient number of personal protective equipment' (74.3%). Logistic regression analyses showed that more negative perception on 'personal protective equipment in the healthcare institutions', 'the confidence in HK's control of COVID-19', 'worried about themselves and friends to suffer this disease' and 'self-perceived risk of infection' indicated higher severity of the four mental health problems (all p < 0.01). The perception on 'public gathering ban', 'the number of isolation wards' and 'expected time to control COVID-19' were significantly associated with PTSD and stress (all p < 0.05). Nurses' perception on government policies and COVID-19 risks played an important role in predicting their mental health status. Policy makers should be aware of nurses' psychological responses and provide timely and targeted emotional support to nurses amid and after the COVID-19 pandemic.

9.
Child Abuse Negl ; 154: 106866, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38852431

RESUMO

BACKGROUND: To examine whether parental corporal punishment is associated with increased risk of concurrent and later sleep disturbances among preschoolers, and whether the association is time-sensitive or dose-responsive. METHODS: This 3-year prospective cohort study used data from the Shanghai Children's Health, Education and Lifestyle Evaluation, Preschool(SCHEDULE-P). Participants were newly enrolled preschoolers in November 2016(wave 1) and followed up in April 2018(wave 2) and April 2019(wave 3). Parents reported the children's corporal punishment experiences and sleep disturbances at each wave survey. Children's risk of sleep disturbances in relation to corporal punishment was examined using logistic regression, adjusting for children's age, gender, emotional/behavioral problems, family annual income, and maternal educational level. RESULTS: The participants of 19,668 children included 9436(47.98 %) females, with a mean age of 3.73(SD = 0.29) years at wave 1. Exposure to corporal punishment was associated with increased odds of concurrent sleep disturbances at wave 1, 2, and 3 (aOR,1.57; 95 % CI, 1.40-1.75; P < .001; aOR,1.60; 95 % CI, 1.43-1.80; P < .001; aOR,1.74; 95 % CI, 1.54-1.95; P < .001), respectively. Exposure to corporal punishment at any wave of preschool was associated with increased odds of sleep disturbances at wave 3, and the risks were greater for proximal and accumulative corporal punishment exposure. CONCLUSION: There is a time-sensitive and dose-responsive association between corporal punishment and sleep disturbance among preschoolers, with greater risk of sleep disturbances for proximal and accumulative exposure of corporal punishment. Promoting positive parenting strategies and avoiding corporal punishment can be a promising strategy to prevent and intervene sleep disturbances in preschoolers.

10.
Adv Drug Deliv Rev ; 211: 115355, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38849004

RESUMO

Mitochondrial genome (mtDNA) independent of nuclear gene is a set of double-stranded circular DNA that encodes 13 proteins, 2 ribosomal RNAs and 22 mitochondrial transfer RNAs, all of which play vital roles in functions as well as behaviors of mitochondria. Mutations in mtDNA result in various mitochondrial disorders without available cures. However, the manipulation of mtDNA via the mitochondria-targeted gene delivery faces formidable barriers, particularly owing to the mitochondrial double membrane. Given the fact that there are various transport channels on the mitochondrial membrane used to transfer a variety of endogenous substances to maintain the normal functions of mitochondria, mitochondrial endogenous substance transport-inspired nanomaterials have been proposed for mitochondria-targeted gene delivery. In this review, we summarize mitochondria-targeted gene delivery systems based on different mitochondrial endogenous substance transport pathways. These are categorized into mitochondrial steroid hormones import pathways-inspired nanomaterials, protein import pathways-inspired nanomaterials and other mitochondria-targeted gene delivery nanomaterials. We also review the applications and challenges involved in current mitochondrial gene editing systems. This review delves into the approaches of mitochondria-targeted gene delivery, providing details on the design of mitochondria-targeted delivery systems and the limitations regarding the various technologies. Despite the progress in this field is currently slow, the ongoing exploration of mitochondrial endogenous substance transport and mitochondrial biological phenomena may act as a crucial breakthrough in the targeted delivery of gene into mitochondria and even the manipulation of mtDNA.

11.
Front Immunol ; 15: 1368487, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846936

RESUMO

Background: Contactin-1 (CNTN1) antibody-positive nodopathy is rare and exhibits distinct clinical symptoms such as tremors and ataxia. However, the mechanisms of these symptoms and the characteristics of the cerebral spinal fluid (CSF) remain unknown. Case presentation: Here, we report a case of recurrent CNTN1 antibody-positive nodopathy. Initially, a 45-year-old woman experiencing numbness in the upper limbs and weakness in the lower limbs was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Eleven years later, her symptoms worsened, and she began to experience tremors and ataxia. Tests for serum CNTN1, GT1a, and GQ1b antibodies returned positive. Subsequently, she was diagnosed with CNTN1 antibody-positive nodopathy and underwent plasmapheresis therapy, although the treatment's efficacy was limited. To gain a deeper understanding of the disease, we conducted a comprehensive literature review, identifying 52 cases of CNTN1 antibody-positive nodopathy to date, with a tremor prevalence of 26.9%. Additionally, we found that the average CSF protein level in CNTN1 antibody-positive nodopathy was 2.57 g/L, with 87% of patients exhibiting a CSF protein level above 1.5 g/L. Conclusion: We present a rare case of recurrent CNTN1 antibody-positive nodopathy. Our findings indicate a high prevalence of tremor (26.9%) and elevated CSF protein levels among patients with CNTN1 antibody-positive nodopathy.


Assuntos
Autoanticorpos , Contactina 1 , Humanos , Feminino , Pessoa de Meia-Idade , Autoanticorpos/sangue , Autoanticorpos/imunologia , Contactina 1/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/sangue , Recidiva , Tremor/imunologia , Tremor/etiologia , Plasmaferese
12.
J Pharm Biomed Anal ; 247: 116265, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38850849

RESUMO

Dingchuan Decoction (DCD) is a traditional Chinese medicine prescription commonly used in the treatment of asthma, but the mechanism of DCD in treating asthma has not yet been determined. In this study, we employed a combination of metabolomics and network pharmacology to investigate the mechanism of DCD in treating asthma. An allergic asthma rat model was induced by ovalbumin (OVA). Metabolomics based on 1H NMR and UHPLC-MS was used to identify differential metabolites and obtain the major metabolic pathways and potential targets. Network pharmacology was utilized to explore potential targets of DCD for asthma treatment. Finally, the results of metabolomics and network pharmacology were integrated to obtain the key targets and metabolic pathways of DCD for the therapy of asthma, and molecular docking was utilized to validate the key targets. A total of 76 important metabolites and 231 potential targets were identified through metabolomics. Using network pharmacology, 184 potential therapeutic targets were obtained. These 184 targets were overlaid with the 231 potential targets obtained through metabolomics and were analyzed in conjunction with metabolic pathways. Ultimately, the key targets were identified as aldehyde dehydrogenase 2 (ALDH2) and amine oxidase copper-containing 3 (AOC3), and the relevant metabolic pathways affected were glycolysis and gluconeogenesis as well as arginine and proline metabolism. Molecular docking showed that the key targets had high affinity with the relevant active ingredients in DCD, which further demonstrated that DCD may exert therapeutic effects by acting on the key targets. The present study demonstrated that DCD can alleviate OVA-induced allergic asthma and that DCD may have a therapeutic effect by regulating intestinal flora and polyamine metabolism through its effects on ALDH2 and AOC3.


Assuntos
Asma , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Metabolômica , Simulação de Acoplamento Molecular , Farmacologia em Rede , Ovalbumina , Ratos Sprague-Dawley , Animais , Asma/tratamento farmacológico , Asma/metabolismo , Metabolômica/métodos , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Farmacologia em Rede/métodos , Masculino , Cromatografia Líquida de Alta Pressão/métodos , Redes e Vias Metabólicas/efeitos dos fármacos , Aldeído-Desidrogenase Mitocondrial/metabolismo , Medicina Tradicional Chinesa/métodos
13.
J Imaging Inform Med ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806952

RESUMO

Personalized management involving heart failure (HF) etiology is crucial for better prognoses. We aim to evaluate the utility of a radiomics nomogram based on gated myocardial perfusion imaging (GMPI) in distinguishing ischemic from non-ischemic origins of HF. A total of 172 heart failure patients with reduced left ventricular ejection fraction (HFrEF) who underwent GMPI scan were divided into training (n = 122) and validation sets (n = 50) based on chronological order of scans. Radiomics features were extracted from the resting GMPI. Four machine learning algorithms were used to construct radiomics models, and the model with the best performances were selected to calculate the Radscore. A radiomics nomogram was constructed based on the Radscore and independent clinical factors. Finally, the model performance was validated using operating characteristic curves, calibration curve, decision curve analysis, integrated discrimination improvement values (IDI), and the net reclassification index (NRI). Three optimal radiomics features were used to build a radiomics model. Total perfusion deficit (TPD) was identified as the independent factors of conventional GMPI metrics for building the GMPI model. In the validation set, the radiomics nomogram integrating the Radscore, age, systolic blood pressure, and TPD significantly outperformed the GMPI model in distinguishing ischemic cardiomyopathy (ICM) from non-ischemic cardiomyopathy (NICM) (AUC 0.853 vs. 0.707, p = 0.038). IDI analysis indicated that the nomogram improved diagnostic accuracy by 28.3% compared to the GMPI model in the validation set. By combining radiomics signatures with clinical indicators, we developed a GMPI-based radiomics nomogram that helps to identify the ischemic etiology of HFrEF.

14.
BMC Public Health ; 24(1): 1432, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811897

RESUMO

BACKGROUND: To explore the relationship between occupational stress, burnout and depressive symptoms among railroad workers in Fuzhou, and to analyze the interaction of burnout and occupational stress on depressive symptoms. METHODS: In this study, 861 railway employees of Fuzhou railway bureau were randomly selected from January to April, 2022. Occupational stress inventory revised edition (OSI-R), China job burnout inventory (CMBI) and Symptom Checklist-90 (SCL-90) were used to investigate the occupational stress, job burnout and depressive symptoms of railway workers. Interactions associated with depressive symptoms were assessed by linear hierarchical regression analysis and SPSS macros (PROCESS). RESULTS: Occupational stress, job burnout and depressive symptoms accounted for 50.58%, 93.47%, and 11.19% of the study population, respectively. There were intergroup differences between age, marriage status, and length of service (P < 0.05). Occupational stress and job burnout are the main risk factors for depressive symptoms (OR: 2.01, 95% CI: 1.17-3.45; 1.94, 1.69-2.23, respectively). More importantly, further analysis of the interaction between occupational stress and job burnout showed that those with high levels of job burnout had a high-risk effect on depressive symptoms at high levels of occupational stress. CONCLUSION: Occupational stress and job burnout are risk factors for depressive symptoms among railroad workers in Fuzhou City. The interaction of job burnout and occupational stress increases the risk of depressive symptoms.


Assuntos
Esgotamento Profissional , Depressão , Estresse Ocupacional , Ferrovias , Humanos , China/epidemiologia , Masculino , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Depressão/epidemiologia , Depressão/psicologia , Adulto , Feminino , Estresse Ocupacional/psicologia , Estresse Ocupacional/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem , Inquéritos e Questionários
15.
Cell Immunol ; 401-402: 104838, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38810591

RESUMO

BACKGROUND: The NOD-like receptor protein 3 (NLRP3) mediated pyroptosis of macrophages is closely associated with liver ischemia reperfusion injury (IRI). As a covalent inhibitor of NLRP3, Oridonin (Ori), has strong anti-inflammasome effect, but its effect and mechanisms for liver IRI are still unknown. METHODS: Mice and liver macrophages were treated with Ori, respectively. Co-IP and LC-MS/MS analysis of the interaction between PKM2 and NLRP3 in macrophages. Liver damage was detected using H&E staining. Pyroptosis was detected by WB, TEM, and ELISA. RESULTS: Ori ameliorated liver macrophage pyroptosis and liver IRI. Mechanistically, Ori inhibited the interaction between pyruvate kinase M2 isoform (PKM2) and NLRP3 in hypoxia/reoxygenation(H/R)-induced macrophages, while the inhibition of PKM2/NLRP3 reduced liver macrophage pyroptosis and liver IRI. CONCLUSION: Ori exerted protective effects on liver IRI via suppressing PKM2/NLRP3-mediated liver macrophage pyroptosis, which might become a potential therapeutic target in the clinic.

16.
Discov Med ; 36(184): 946-958, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38798254

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) commonly impacts fertile females with potentially severe effects on fertility and metabolism. Blood ghrelin levels are lower in PCOS patients, and exogenous supplements have been proposed for their potential to trigger anti-inflammatory effects at the cellular level. This study aimed to investigate whether pretreatment with ghrelin reduced inflammation, insulin resistance, and reproductive abnormalities in PCOS and the underlying mechanism of this disorder. METHODS: Ghrelin supplementation was first tested in an inflammation model using human ovarian granulosa cells (KGN cells) that were built by treated with Lipolyaccharide. KGN cells were pretreated with ghrelin and exposed to lipopolysaccharide (LPS). Inflammatory gene expression and cytokine production were analyzed by Enzyme-linked immunosorbent assay (ELISA). Based on these results, the PCOS mice model was built with Dehydroepiandrosterone (DHEA) and a high-fat diet. The mRNA and protein expressions of inflammatory factors including Toll-like receptor 4 (TLR4), nuclear factor kappa-B-p65 (NF-κB-p65), Phospho-NF-κB-p65 (p-NF-κB-p65) and myeloid differentiation factor 88 (MYD88) related to the TLR4/NF-κB signaling pathway were evaluated in KGN cells and mouse ovarian tissues using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) and western blot, respectively. Lipid metabolism was quantified via an automated biochemical analyzer. RESULTS: The mRNA and protein expressions of interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), and tumor necrosis factor alpha (TNF-α) in ghrelin pretreated KGN cells were lower than the LPS group (p < 0.05). Protein expression was reduced for TLR4, NF-κB-p65, and MYD88 within KGN cells of ghrelin groups compared to the LPS group (p < 0.05). Ghrelin treatment restored the estrous cycle and slowed weight gain and abdominal fat weight of PCOS mice (p < 0.05). Ghrelin treatment decreased the serum concentrations of testosterone, luteinizing hormone, insulin, IL-6, IL-1ß, and TNF-α compared to the PCOS group (p < 0.05). Estradiol concentrations of mice treated with ghrelin were higher than the PCOS group (p < 0.05). The concentrations of low and high-density lipoprotein, triglyceride, and cholesterol in mice treated with ghrelin were lower than in the PCOS mice (p < 0.05). Inflammatory gene expression for IL-6, IL-1ß, TNF-α, TLR4, NF-κB-p65, and MYD88 decreased in the ovarian tissues of ghrelin-treated mice compared to the PCOS group (p < 0.05), along with reduced protein expression of TLR4, p-NF-κB-p65, and MYD88 (p < 0.05). CONCLUSIONS: In the present study, ghrelin treatment effectively reduced inflammation in vitro, and attenuated insulin resistance and reproductive abnormalities in PCOS mice through the TLR4/NF-κB signaling pathway, highlighting potential therapeutic avenues for future PCOS treatments and research directions.


Assuntos
Grelina , Inflamação , Resistência à Insulina , NF-kappa B , Síndrome do Ovário Policístico , Transdução de Sinais , Receptor 4 Toll-Like , Animais , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/patologia , Feminino , Receptor 4 Toll-Like/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , NF-kappa B/metabolismo , Inflamação/metabolismo , Humanos , Modelos Animais de Doenças , Células da Granulosa/metabolismo , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/patologia
17.
Int J Mol Sci ; 25(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38791374

RESUMO

Cryptococcus neoformans (C. neoformans) is a pathogenic fungus that can cause life-threatening meningitis, particularly in individuals with compromised immune systems. The current standard treatment involves the combination of amphotericin B and azole drugs, but this regimen often leads to inevitable toxicity in patients. Therefore, there is an urgent need to develop new antifungal drugs with improved safety profiles. We screened antimicrobial peptides from the hemolymph transcriptome of Blaps rhynchopetera (B. rhynchopetera), a folk Chinese medicine. We found an antimicrobial peptide named blap-6 that exhibited potent activity against bacteria and fungi. Blap-6 is composed of 17 amino acids (KRCRFRIYRWGFPRRRF), and it has excellent antifungal activity against C. neoformans, with a minimum inhibitory concentration (MIC) of 0.81 µM. Blap-6 exhibits strong antifungal kinetic characteristics. Mechanistic studies revealed that blap-6 exerts its antifungal activity by penetrating and disrupting the integrity of the fungal cell membrane. In addition to its direct antifungal effect, blap-6 showed strong biofilm inhibition and scavenging activity. Notably, the peptide exhibited low hemolytic and cytotoxicity to human cells and may be a potential candidate antimicrobial drug for fungal infection caused by C. neoformans.


Assuntos
Antifúngicos , Peptídeos Antimicrobianos , Besouros , Cryptococcus neoformans , Testes de Sensibilidade Microbiana , Cryptococcus neoformans/efeitos dos fármacos , Animais , Antifúngicos/farmacologia , Antifúngicos/química , Besouros/microbiologia , Besouros/efeitos dos fármacos , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Humanos , Biofilmes/efeitos dos fármacos , Sequência de Aminoácidos
18.
J Ethnopharmacol ; 331: 118290, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38703872

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: HuoXueTongFu Formula (HXTF) is a traditional Chinese herbal formula that has been used as a supplement and alternative therapy for intraperitoneal adhesion (IA). However, its specific mechanism of action has not been fully understood. AIM OF THE STUDY: In surgery, IA presents an inevitable challenge, significantly impacting patients' physical and mental well-being and increasing the financial burden. Our previous research has confirmed the preventive effects of HXTF on IA formation. However, the precise mechanism of its action still needs to be understood. METHODS: In this study, the IA model was successfully established by using the Ischemic buttons and treated with HXTF for one week with or without Mer Tyrosine Kinase (MerTK) inhibitor. We evaluated the pharmacodynamic effect of HXTF on IA mice. The MerTK/phosphoinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway-associated proteins were detected by Western blotting. Neutrophil extracellular traps (NETs) were detected by immunofluorescence. Macrophage phenotype was assessed by immunohistochemistry and flow cytometry. Inflammatory cytokines were detected by Real Time Quantitative PCR and Western blotting. RESULTS: HXTF reduced inflammatory response and alleviated IA. HXTF significantly enhanced MerTK expression, increased the number of M2c macrophages, and decreased the formation of NETs. In addition, the MerTK/PI3K/AKT pathway was significantly activated by HXTF. However, after using MerTK inhibitors, the role of HXTF in inducing M2c macrophage through activation of the PI3K/AKT pathway was suppressed and there was no inhibitory effect on NETs formation and inflammatory responses, resulting in diminished inhibition of adhesion. CONCLUSION: HXTF may improve IA by activating the MerTK/PI3K/AKT pathway to induce M2c polarization, which removes excess NETs and attenuates the inflammatory response.


Assuntos
Medicamentos de Ervas Chinesas , Macrófagos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , c-Mer Tirosina Quinase , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , c-Mer Tirosina Quinase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Aderências Teciduais/prevenção & controle , Aderências Teciduais/metabolismo , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/metabolismo , Modelos Animais de Doenças
19.
Bioresour Technol ; 402: 130779, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38701977

RESUMO

Submerged macrophytes are effective in ecological restoration of water bodies polluted by nitrogen and phosphorus, and its restoration capacity depends on underwater illumination condition. This study explored the influencing mechanism of illumination on Vallisneria spinulosa Yan (V. spinulosa Yan) for water restoration. Addition of underwater light source increased the total nitrogen, ammonia nitrogen, total phosphorus, and phosphate removal loads of the V. spinulosa Yan growth system by 61.5, 39.2, 8.5, and 5.0 mg m-2 d-1, respectively. Meanwhile, the growth of V. spinulosa Yan was obviously promoted, even with high water turbidity. Although the biological nitrogen removal processes were inhibited by adding underwater light source, the growth of V. spinulosa Yan can be significantly improved, thus enhancing the efficiency of water purification via the absorption of nitrogen and phosphorus by V. spinulosa Yan. This study provides a theoretical foundation and technical support for application of submerged macrophytes in ecological water restoration.


Assuntos
Luz , Nitrogênio , Fósforo , Rizosfera , Purificação da Água , Purificação da Água/métodos , Hydrocharitaceae/metabolismo , Hydrocharitaceae/crescimento & desenvolvimento , Biodegradação Ambiental , Água , Ecossistema
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