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1.
J Asian Nat Prod Res ; : 1-7, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38975972

RESUMO

A chemical investigation on the roots of Aconitum nagarum afforded two undescribed C19-diterpenoid alkaloids nagarumines D and E (1 and 2). The structures of the new compounds were elucidated by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, as well as HR-ESI-MS. The two isolated alkaloids were tested in vitro for cytotoxic activity against five gastric tumor cell lines. Consequently, compound 2 exhibited some cytotoxicities against several human cancer cell lines with IC50 value less than 20.0 µM.

2.
Stem Cell Res Ther ; 15(1): 194, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956719

RESUMO

BACKGROUND: Repairation of bone defects remains a major clinical problem. Constructing bone tissue engineering containing growth factors, stem cells, and material scaffolds to repair bone defects has recently become a hot research topic. Nerve growth factor (NGF) can promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but the low survival rate of the BMSCs during transplantation remains an unresolved issue. In this study, we investigated the therapeutic effect of BMSCs overexpression of NGF on bone defect by inhibiting pyroptosis. METHODS: The relationship between the low survival rate and pyroptosis of BMSCs overexpressing NGF in localized inflammation of fractures was explored by detecting pyroptosis protein levels. Then, the NGF+/BMSCs-NSA-Sca bone tissue engineering was constructed by seeding BMSCs overexpressing NGF on the allograft bone scaffold and adding the pyroptosis inhibitor necrosulfonamide(NSA). The femoral condylar defect model in the Sprague-Dawley (SD) rat was studied by micro-CT, histological, WB and PCR analyses in vitro and in vivo to evaluate the regenerative effect of bone repair. RESULTS: The pyroptosis that occurs in BMSCs overexpressing NGF is associated with the nerve growth factor receptor (P75NTR) during osteogenic differentiation. Furthermore, NSA can block pyroptosis in BMSCs overexpression NGF. Notably, the analyses using the critical-size femoral condylar defect model indicated that the NGF+/BMSCs-NSA-Sca group inhibited pyroptosis significantly and had higher osteogenesis in defects. CONCLUSION: NGF+/BMSCs-NSA had strong osteogenic properties in repairing bone defects. Moreover, NGF+/BMSCs-NSA-Sca mixture developed in this study opens new horizons for developing novel tissue engineering constructs.


Assuntos
Células-Tronco Mesenquimais , Fator de Crescimento Neural , Osteogênese , Ratos Sprague-Dawley , Alicerces Teciduais , Animais , Fator de Crescimento Neural/metabolismo , Fator de Crescimento Neural/genética , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Ratos , Alicerces Teciduais/química , Regeneração Óssea , Aloenxertos , Masculino , Engenharia Tecidual/métodos , Piroptose , Sulfonamidas/farmacologia , Diferenciação Celular , Transplante de Células-Tronco Mesenquimais/métodos , Transplante Ósseo/métodos
3.
MycoKeys ; 106: 173-200, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948915

RESUMO

Zhujiangyuan Nature Reserve, located in Qujing City, Yunnan Province, China, is reported with high fauna and floral diversity, while the fungal diversity of the region is poorly documented. During the summer season in 2023, decaying wood-inhabiting microfungi were collected from different microhabitats. The novel species were identified based on morphological characteristics and phylogenetic analyses (based on combined datasets of ITS, LSU, SSU, tef1-α, and rpb2 regions). Two species belong to Dothideomycetes (viz., Spegazziniazhujiangyuanensis sp. nov. and Phaeoseptumzhujiangyuanense sp. nov. in Pleosporales) while the other one resides in Sordariomycetes (Synnemasporellafanii sp. nov. in Diaporthales). The results are in conformity with the earlier studies that predicted higher fungal diversity in this region.

4.
Mol Ther Oncol ; 32(2): 200816, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38948919

RESUMO

The presence of a poly(A) tail is indispensable for the post-transcriptional regulation of gene expression in cancer. This dynamic and modifiable feature of transcripts is under the control of various nuclear and cytoplasmic proteins. This study aimed to develop a novel cytoplasmic poly(A)-related signature for predicting prognosis, clinical attributes, tumor immune microenvironment (TIME), and treatment response in hepatocellular carcinoma (HCC). Utilizing RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA), non-negative matrix factorization (NMF), and principal-component analysis (PCA) were employed to categorize HCC patients into three clusters, thus demonstrating the pivotal prognostic role of cytoplasmic poly(A) tail regulators. Furthermore, machine learning algorithms such as least absolute shrinkage and selection operator (LASSO), survival analysis, and Cox proportional hazards modeling were able to distinguish distinct cytoplasmic poly(A) subtypes. As a result, a 5-gene signature derived from TCGA was developed and validated using International Cancer Genome Consortium (ICGC) HCC datasets. This novel classification based on cytoplasmic poly(A) regulators has the potential to improve prognostic predictions and provide guidance for chemotherapy, immunotherapy, and transarterial chemoembolization (TACE) in HCC.

5.
CNS Neurosci Ther ; 30(7): e14829, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38961264

RESUMO

AIMS: Paclitaxel (PTX) is extensively utilized in the management of diverse solid tumors, frequently resulting in paclitaxel-induced peripheral neuropathy (PIPN). The present study aimed to investigate sex differences in the behavioral manifestations and underlying pathogenesis of PIPN and search for clinically efficacious interventions. METHODS: Male and female C57BL/6 mice (5-6 weeks and 12 months, weighing 18-30 g) were intraperitoneally (i.p.) administered paclitaxel diluted in saline (NaCl 0.9%) at a dose of 2 mg/kg every other day for a total of 4 injections. Von Frey and hot plate tests were performed before and after administration to confirm the successful establishment of the PIPN model and also to evaluate the pain of PIPN and the analgesic effect of PD-L1. On day 14 after PTX administration, PD-L1 protein (10 ng/pc) was injected into the PIPN via the intrathecal (i.t.) route. To knock down TRPV1 in the spinal cord, adeno-associated virus 9 (AAV9)-Trpv1-RNAi (5 µL, 1 × 1013 vg/mL) was slowly injected via the i.t. route. Four weeks after AAV9 delivery, the downregulation of TRPV1 expression was verified by immunofluorescence staining and Western blotting. The levels of PD-L1, TRPV1 and CGRP were measured via Western blotting, RT-PCR, and immunofluorescence staining. The levels of TNF-α and IL-1ß were measured via RT-PCR. RESULTS: TRPV1 and CGRP protein and mRNA levels were higher in the spinal cords of control female mice than in those of control male mice. PTX-induced nociceptive behaviors in female PIPN mice were greater than those in male PIPN mice, as indicated by increased expression of TRPV1 and CGRP. The analgesic effects of PD-L1 on mechanical hyperalgesia and thermal sensitivity were significantly greater in female mice than in male mice, with calculated relative therapeutic levels increasing by approximately 2.717-fold and 2.303-fold, respectively. PD-L1 and CGRP were partly co-localized with TRPV1 in the dorsal horn of the mouse spinal cord. The analgesic effect of PD-L1 in PIPN mice was observed to be mediated through the downregulation of TRPV1 and CGRP expression following AAV9-mediated spinal cord specific decreased TRPV1 expression. CONCLUSIONS: PTX-induced nociceptive behaviors and the analgesic effect of PD-L1 in PIPN mice were sexually dimorphic, highlighting the significance of incorporating sex as a crucial biological factor in forthcoming mechanistic studies of PIPN and providing insights for potential sex-specific therapeutic approaches.


Assuntos
Antígeno B7-H1 , Peptídeo Relacionado com Gene de Calcitonina , Camundongos Endogâmicos C57BL , Paclitaxel , Doenças do Sistema Nervoso Periférico , Caracteres Sexuais , Canais de Cátion TRPV , Animais , Paclitaxel/toxicidade , Masculino , Feminino , Camundongos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Antineoplásicos Fitogênicos/toxicidade , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo
6.
Org Lett ; 26(27): 5827-5832, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38954473

RESUMO

We disclosed herein an enantioselective formal siloxycarbene insertion reaction enabled by chiral phosphoric acid and blue LED irradiation. This is the first time the asymmetric siloxycarbene insertion into an sp3 C-H bond under transition-metal free conditions has been realized. The reaction features good isolated yields (up to 92%), high enantioselectivity (up to 99:1 er), mild reaction conditions, and good compatibility. Moreover, this method also provides a green and efficient method to construct a chiral quaternary carbon center.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39023508

RESUMO

An efficient interface and composition modification strategy is proposed to significantly increase the rate capacity and initial Coulombic efficiency (ICE) of SnO anodes via energy band structure modulation for Na-ion batteries (SIBs). The as-fabricated SnO@Bi@C material with Bi nanocrystals homogeneously dispersed on and around the SnO surface is prepared by an electrospinning method. The excellently dispersed Bi nanocrystals realize an effective interface contact with SnO and Na2O, which effectively lowers the electron conduction barriers and promotes sodium-ion release and transport upon the desodiation process, increasing the rate capacity and ICE of the SnO anode. The prepared SnO@Bi@C exhibits a much higher rate capacity up to 10 A g-1, except an improved ICE of 80.67%, compared to 57.38% of SnO@C. Importantly, the intercalation of Na+ between layer-structured Bi galleries provides a good basis for excellent cycle stability due to the highways constructed inside the prepared composites. This finding provides an effective tactic to establish ion transport high-speed channels, which essentially increase the rate performance and the ICE of the SnO-based anodes.

8.
J Hepatocell Carcinoma ; 11: 1193-1206, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38946842

RESUMO

Purpose: The impact of visceral adiposity on overall survival (OS) in hepatocellular carcinoma (HCC) receiving immunotherapy was unclear. We aimed to determine how visceral adiposity affected OS and explore the interrelationships between visceral adiposity, body mass index (BMI), and other body compositions. Patients and Methods: Data from three centers were retrospectively analyzed. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were used to define each body composition. The BMI subgroups included the underweight, the normal weight, and the obesity. The Log rank test compared survival curves calculated by the Kaplan-Meier method. The relationships between body compositions and BMI with OS were examined using Cox proportional risk regression models. Results: A total of 305 patients who met the criteria were included. Patients with low VATI had significantly worse OS (P = 0.001). The protections of VATI (P = 0.011) on OS were independent of covariates. However, after additional adjustment of SMI, the effect of VATI on OS disappeared (P = 0.146), but the effect of SMD on OS did not (P = 0.021). BMI has a significant U-shaped relationship with OS, and the effect of BMI on OS equally disappeared after additional adjustment by SMI. Conclusion: This study first demonstrated that high VATI and mid-level BMI were protective for the survival of patients with HCC receiving immunotherapy. Skeletal muscle status (including SMI and SMD) may be the better predictor for outcomes of patients with HCC receiving immunotherapy.

9.
Plant Cell Environ ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946254

RESUMO

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

10.
Adv Sci (Weinh) ; : e2307224, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946607

RESUMO

Targeting NLRP3 inflammasome has been recognized as a promising therapeutic strategy for the treatment of numerous common diseases. UK5099, a long-established inhibitor of mitochondrial pyruvate carrier (MPC), is previously found to inhibit macrophage inflammatory responses independent of MPC expression. However, the mechanisms by which UK5099 inhibit inflammatory responses remain unclear. Here, it is shown that UK5099 is a potent inhibitor of the NLRP3 inflammasome in both mouse and human primary macrophages. UK5099 selectively suppresses the activation of the NLRP3 but not the NLRC4 or AIM2 inflammasomes. Of note, UK5099 retains activities on NLRP3 in macrophages devoid of MPC expression, indicating this inhibitory effect is MPC-independent. Mechanistically, UK5099 abrogates mitochondria-NLRP3 interaction and in turn inhibits the assembly of the NLRP3 inflammasome. Further, a single dose of UK5099 persistently reduces IL-1ß production in an endotoxemia mouse model. Importantly, structure modification reveals that the inhibitory activities of UK5099 on NLRP3 are unrelated to the existence of the activated double bond within the UK5099 molecule. Thus, this study uncovers a previously unknown molecular target for UK5099, which not only offers a new candidate for the treatment of NLRP3-driven diseases but also confounds its use as an MPC inhibitor in immunometabolism studies.

11.
J Hazard Mater ; 476: 135048, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964041

RESUMO

While the cardiovascular system is a primary target of organophosphorus flame retardants (OPFRs), particularly aryl-OPFRs, it is still exclusive whether the diisodecyl phenyl phosphate (DIDPP), widely used and broadly present in the environment at high concentrations, elicits atherosclerosis effects. Liver X receptors (LXRs) play a direct role in regulating the formation of atherosclerotic lesions. This study was the first to demonstrate that DIDPP acts as an LXRα ligand and functions as an LXRα antagonist with a half-maximal inhibitory concentration of 16.2 µM. We showed that treatment of an in vitro macrophage model with 1 to 10 µM of DIDPP resulted in the downregulation of direct targets of LXRα, namely ABCA1, ABCG1 and SR-B1, thereby leading to a 7.9-13.2 % reduction in cholesterol efflux. This caused dose-dependent, 24.1-43.1 % increases in the staining intensity of foam cells in the macrophage model. This atherosclerotic effect of DIDPP was proposed to be due to its antagonism of LXRα activity, as DIDPP treatment did not alter cholesterol influx. In conclusion, the findings of this study demonstrate that exposure to DIDPP may be a risk factor for atherosclerosis due to the LXRα-antagonistic activity of DIDPP and its ubiquity in the environment.

12.
Sci Rep ; 14(1): 15202, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956148

RESUMO

This study aimed to develop and internally validate a nomogram model for assessing the risk of intraoperative hypothermia in patients undergoing video-assisted thoracoscopic (VATS) lobectomy. This study is a retrospective study. A total of 530 patients who undergoing VATS lobectomy from January 2022 to December 2023 in a tertiary hospital in Wuhan were selected. Patients were divided into hypothermia group (n = 346) and non-hypothermia group (n = 184) according to whether hypothermia occurred during the operation. Lasso regression was used to screen the independent variables. Logistic regression was used to analyze the risk factors of hypothermia during operation, and a nomogram model was established. Bootstrap method was used to internally verify the nomogram model. Receiver operating characteristic (ROC) curve was used to evaluate the discrimination of the model. Calibration curve and Hosmer Lemeshow test were used to evaluate the accuracy of the model. Decision curve analysis (DCA) was used to evaluate the clinical utility of the model. Intraoperative hypothermia occurred in 346 of 530 patients undergoing VATS lobectomy (65.28%). Logistic regression analysis showed that age, serum total bilirubin, inhaled desflurane, anesthesia duration, intraoperative infusion volume, intraoperative blood loss and body mass index were risk factors for intraoperative hypothermia in patients undergoing VATS lobectomy (P < 0.05). The area under ROC curve was 0.757, 95% CI (0.714-0.799). The optimal cutoff value was 0.635, the sensitivity was 0.717, and the specificity was 0.658. These results suggested that the model was well discriminated. Calibration curve has shown that the actual values are generally in agreement with the predicted values. Hosmer-Lemeshow test showed that χ2 = 5.588, P = 0.693, indicating that the model has a good accuracy. The DCA results confirmed that the model had high clinical utility. The nomogram model constructed in this study showed good discrimination, accuracy and clinical utility in predicting patients with intraoperative hypothermia, which can provide reference for medical staff to screen high-risk of intraoperative hypothermia in patients undergoing VATS lobectomy.


Assuntos
Hipotermia , Nomogramas , Cirurgia Torácica Vídeoassistida , Humanos , Masculino , Feminino , Cirurgia Torácica Vídeoassistida/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Hipotermia/etiologia , Idoso , Fatores de Risco , Curva ROC , Pneumonectomia , Complicações Intraoperatórias/etiologia , Neoplasias Pulmonares/cirurgia , Adulto , Modelos Logísticos
13.
Bioorg Med Chem ; : 117788, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38964974

RESUMO

Ovarian cancer is a common malignant tumor in women, and 70 % of ovarian cancer patients are diagnosed at an advanced stage. Drug chemotherapy is an important method for treating ovarian cancer, but recurrence and chemotherapy resistance often lead to treatment failure. In this study, we screened 10 extracts of Tripterygium wilfordii, a traditional Chinese herb, and found that triptonide had potent anti-ovarian cancer activity and an IC50 of only 3.803 nM against A2780 cell lines. In addition, we determined that triptonide had a better antitumor effect on A2780 cell lines than platinum chemotherapeutic agents in vitro and that triptonide had no significant side effects in vivo. We found that triptonide induced apoptosis in ovarian cancer cells through activation of the p38/p53 pathway and it also induced cell cycle arrest at the S phase. In addition, we demonstrated that triptonide could activate lethal autophagy, which led to growth inhibition and cell death in ovarian cancer cells, resulting in an anti-ovarian cancer effect. Triptonide exerts its anti-ovarian cancer effect through activation of the p38/p53 pathway and induction of autophagy to promote apoptosis, which provides a new candidate drug and strategy for the treatment of ovarian cancer.

15.
Eur J Surg Oncol ; 50(9): 108481, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38959845

RESUMO

INTRODUCTION: We aimed to compare early postoperative patient-reported outcomes between multiportal robotic-assisted thoracoscopic surgery (M-RATS) and uniportal video-assisted thoracoscopic surgery (U-VATS) for non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Symptom severity and functional status were measured using the Perioperative Symptom Assessment for Lung Surgery at pre-surgery, during postoperative hospitalisation, and within 4 weeks of discharge. A propensity score-matched (PSM) analysis of patients with NSCLC who were treated with M-RATS and U-VATS was performed. The symptom severity and daily functional status presented as proportion of moderate-to-severe scores on a 0-10-point scale, were compared using a generalised estimation equation model. RESULTS: We enrolled 762 patients with NSCLC from a prospective cohort (CN-PRO-Lung 3), including 151 and 611 who underwent M-RATS and U-VATS, respectively, before PSM analysis. After 1:1 PSM, two groups of 148 patients each were created. Pain severity (P = 0.019) and activity limitation (P = 0.001) during hospitalisation were higher in the M-RATS group. However, no significant differences existed post-discharge in pain (P = 0.383), cough (P = 0.677), shortness of breath (P = 0.526), disturbed sleep (P = 0.525), drowsiness (P = 0.304), fatigue (P = 0.153), distress (P = 0.893), walking difficulty (P = 0.242), or activity limitation (P = 0.513). M-RATS caused less intraoperative blood loss (P = 0.013), more stations of dissected lymph nodes (P = 0.001), more numbers of dissected lymph nodes (P = 0.001), and less tube drainage on the first postoperative day (P = 0.003) than U-VATS. CONCLUSION: M-RATS and U-VATS achieved comparable symptom burden and functional impairment after discharge. However, compared to U-VATS, M-RATS was associated with more severe pain and activity limitation in the short postoperative period. TRIAL REGISTRATION NUMBER: ChiCTR2000033016.

16.
Bioorg Med Chem ; 110: 117825, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38954918

RESUMO

To date, the US Food and Drug Administration (FDA) has approved six small interfering RNA (siRNA) drugs: patisiran, givosiran, lumasiran, inclisiran, vutrisiran, and nedosiran, serving as compelling evidence of the promising potential of RNA interference (RNAi) therapeutics. The successful implementation of siRNA therapeutics is improved through a combination of various chemical modifications and diverse delivery approaches. The utilization of chemically modified siRNA at specific sites on either the sense strand (SS) or antisense strand (AS) has the potential to enhance resistance to ribozyme degradation, improve stability and specificity, and prolong the efficacy of drugs. Herein, we provide comprehensive analyses concerning the correlation between chemical modifications and structure-guided siRNA design. Various modifications, such as 2'-modifications, 2',4'-dual modifications, non-canonical sugar modifications, and phosphonate mimics, are crucial for the activity of siRNA. We also emphasize the essential strategies for enhancing overhang stability, improving RISC loading efficacy and strand selection, reducing off-target effects, and discussing the future of targeted delivery.

17.
Sensors (Basel) ; 24(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39000905

RESUMO

In the electronic nose (E-nose) systems, gas type recognition and accurate concentration prediction are some of the most challenging issues. This study introduced an innovative pattern recognition method of time-frequency attention convolutional neural network (TFA-CNN). A time-frequency attention block was designed in the network, aiming to excavate and effectively integrate the temporal and frequency domain information in the E-nose signals to enhance the performance of gas classification and concentration prediction tasks. Additionally, a novel data augmentation strategy was developed, manipulating the feature channels and time dimensions to reduce the interference of sensor drift and redundant information, thereby enhancing the model's robustness and adaptability. Utilizing two types of metal-oxide-semiconductor gas sensors, this research conducted qualitative and quantitative analysis on five target gases. The evaluation results showed that the classification accuracy could reach 100%, and the coefficient of the determination (R2) score of the regression task was up to 0.99. The Pearson correlation coefficient (r) was 0.99, and the mean absolute error (MAE) was 1.54 ppm. The experimental test results were almost consistent with the system predictions, and the MAE was 1.39 ppm. This study provides a method of network learning that combines time-frequency domain information, exhibiting high performance in gas classification and concentration prediction within the E-nose system.

18.
Respir Res ; 25(1): 276, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39010105

RESUMO

BACKGROUND: The pathogenesis of acute lung injury (ALI) involves a severe inflammatory response, leading to significant morbidity and mortality. N6-methylation of adenosine (m6A), an abundant mRNA nucleotide modification, plays a crucial role in regulating mRNA metabolism and function. However, the precise impact of m6A modifications on the progression of ALI remains elusive. METHODS: ALI models were induced by either intraperitoneal injection of lipopolysaccharide (LPS) into C57BL/6 mice or the LPS-treated alveolar type II epithelial cells (AECII) in vitro. The viability and proliferation of AECII were assessed using CCK-8 and EdU assays. The whole-body plethysmography was used to record the general respiratory functions. M6A RNA methylation level of AECII after LPS insults was detected, and then the "writer" of m6A modifications was screened. Afterwards, we successfully identified the targets that underwent m6A methylation mediated by METTL3, a methyltransferase-like enzyme. Last, we evaluated the regulatory role of METTL3-medited m6A methylation at phosphatase and tensin homolog (Pten) in ALI, by assessing the proliferation, viability and inflammation of AECII. RESULTS: LPS induced marked damages in respiratory functions and cellular injuries of AECII. The m6A modification level in mRNA and the expression of METTL3, an m6A methyltransferase, exhibited a notable rise in both lung tissues of ALI mice and cultured AECII cells subjected to LPS treatment. METTL3 knockdown or inhibition improved the viability and proliferation of LPS-treated AECII, and also reduced the m6A modification level. In addition, the stability and translation of Pten mRNA were enhanced by METTL3-mediated m6A modification, and over-expression of PTEN reversed the protective effect of METTL3 knockdown in the LPS-treated AECII. CONCLUSIONS: The progression of ALI can be attributed to the elevated levels of METTL3 in AECII, as it promotes the stability and translation of Pten mRNA through m6A modification. This suggests that targeting METTL3 could offer a novel approach for treating ALI.


Assuntos
Lesão Pulmonar Aguda , Células Epiteliais Alveolares , Proliferação de Células , Metiltransferases , Camundongos Endogâmicos C57BL , PTEN Fosfo-Hidrolase , RNA Mensageiro , Animais , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/patologia , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , Metiltransferases/metabolismo , Metiltransferases/genética , Camundongos , Proliferação de Células/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/patologia , Masculino , RNA Mensageiro/metabolismo , Sobrevivência Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Metilação , Adenosina/análogos & derivados , Adenosina/metabolismo , Lipopolissacarídeos/toxicidade , Estabilidade de RNA , Células Cultivadas
19.
World J Clin Cases ; 12(20): 4154-4165, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39015913

RESUMO

BACKGROUND: Accurate condition assessment is critical for improving the prognosis of neonatal respiratory distress syndrome (RDS), but current assessment methods for RDS pose a cumulative risk of harm to neonates. Thus, a less harmful method for assessing the health of neonates with RDS is needed. AIM: To analyze the relationships between pulmonary ultrasonography and respiratory distress scores, oxygenation index, and chest X-ray grade of neonatal RDS to identify predictors of neonatal RDS severity. METHODS: This retrospective study analyzed the medical information of 73 neonates with RDS admitted to the neonatal intensive care unit of Liupanshui Maternal and Child Care Service Center between April and December 2022. The pulmonary ultrasonography score, respiratory distress score, oxygenation index, and chest X-ray grade of each newborn before and after treatment were collected. Spearman correlation analysis was performed to determine the relationships among these values and neonatal RDS severity. RESULTS: The pulmonary ultrasonography score, respiratory distress score, oxygenation index, and chest X-ray RDS grade of the neonates were significantly lower after treatment than before treatment (P < 0.05). Spearman correlation analysis showed that before and after treatment, the pulmonary ultrasonography score of neonates with RDS was positively correlated with the respiratory distress score, oxygenation index, and chest X-ray grade (ρ = 0.429-0.859, P < 0.05). Receiver operating characteristic curve analysis indicated that pulmonary ultrasonography screening effectively predicted the severity of neonatal RDS (area under the curve = 0.805-1.000, P < 0.05). CONCLUSION: The pulmonary ultrasonography score was significantly associated with the neonatal RDS score, oxygenation index, and chest X-ray grade. The pulmonary ultrasonography score was an effective predictor of neonatal RDS severity.

20.
Environ Sci Pollut Res Int ; 31(32): 45192-45203, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38961018

RESUMO

Exposure to organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) has been reported to be associated with renal impairment and chronic kidney disease (CKD). Nevertheless, the research results thus far have exhibited inconsistency, and the effect of lifestyle on their association is not clear. In this study, we assessed the correlation between serum OCPs/PCBs and CKD and renal function indicators including estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) among 1721 Chinese adults. In order to further investigate the potential impact of lifestyle, we conducted joint associations of lifestyle and OCPs/PCBs on CKD. We found a negative correlation between p,p'-DDE and eGFR, while logistic regression results showed a positive correlation between PCB-153 and CKD (OR, 1.92; 95% CI, 1.21, 3.06). Quantile g-computation regression analyses showed that the association between co-exposure to OCPs/PCBs and CKD was not significant, but p,p'-DDE and PCB-153 were the main contributors to the negative and positive co-exposure effects of eGFR and CKD, respectively, which is consistent with the regression results. Participants with both relatively high PCB-153 exposure and an unhealthy lifestyle had the highest risk of CKD, in the joint association analysis. The observed associations were generally supported by the FAS-eGFR method. Our research findings suggest that exposure to OCPs/PCBs may be associated with decreased eGFR and increased prevalence of CKD in humans, and a healthy lifestyle can to some extent alleviate the adverse association between PCB-153 exposure and CKD.


Assuntos
Hidrocarbonetos Clorados , Estilo de Vida , Praguicidas , Bifenilos Policlorados , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/epidemiologia , Bifenilos Policlorados/sangue , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Exposição Ambiental , Taxa de Filtração Glomerular , China , Idoso , Poluentes Ambientais
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