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1.
Org Lett ; 26(27): 5609-5613, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38949378

RESUMO

A general intermolecular polarity-mismatched carboamination reaction of unactivated alkenes with unactivated alkyl halides has been developed. A series of nonactivated alkyl-substituted aziridines were constructed in exclusive regioselectivity. The dual polarity-mismatched mechanism might be involved.

2.
Oncol Rep ; 52(2)2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38940341

RESUMO

Intrahepatic cholangiocarcinoma (ICC) is a type of liver cancer associated with poor prognosis and increased mortality; the limited treatment strategy highlights the urgent need for investigation. Traditional Chinese Medicine (TCM), used alone or in combination with other treatments, can enhance therapeutic efficacy, improve life quality of patients and extend overall survival. In total, two rounds of screening of a TCM library of 2,538 active compounds were conducted using a Cell Counting Kit­8 assay and ICC cell lines. Cell proliferation and migration abilities were assessed through colony formation, 5­ethynyl­2'­deoxyuridine, would healing and Transwell assays. The impact of digitoxin (DT) on signaling pathways was initially investigated using RNA sequencing and further validated using reverse transcription­quantitative PCR, western blotting, lectin blotting and flow cytometry. ICC cells stably overexpressing ST6 ß­galactoside α­2,6­sialyltransferase 1 (ST6GAL1) were generated through lentiviral transfection. It was shown that DT emerged as a highly effective anti­ICC candidate from two rounds high­throughput library screening. DT could inhibit the proliferation and migration of ICC cells by suppressing NF­κB activation and reducing nuclear phosphorylated­NF­κB levels, along with diminishing ST6GAL1 mRNA and protein expression. The aforementioned biological effects and signal pathways of DT could be counteracted by overexpressing ST6GAL1 in ICC cells. In conclusion, DT suppressed ICC cell proliferation and migration by targeting the NF­κB/ST6GAL1 signaling axis. The findings of the present study indicated the promising therapeutic effects of DT in managing ICC, offering new avenues for treatment strategies.


Assuntos
Neoplasias dos Ductos Biliares , Movimento Celular , Proliferação de Células , Colangiocarcinoma , Digitoxina , NF-kappa B , Sialiltransferases , Transdução de Sinais , Humanos , Transdução de Sinais/efeitos dos fármacos , NF-kappa B/metabolismo , Proliferação de Células/efeitos dos fármacos , Sialiltransferases/genética , Sialiltransferases/metabolismo , Digitoxina/farmacologia , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Colangiocarcinoma/metabolismo , Colangiocarcinoma/genética , Movimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/genética , Antígenos CD/metabolismo , Antígenos CD/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , beta-D-Galactosídeo alfa 2-6-Sialiltransferase
3.
Front Microbiol ; 15: 1302907, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827158

RESUMO

Background: Sepsis is commonly associated with a sudden impairment of brain function, thus leading to significant rates of illness and mortality. The objective of this research was to integrate microbiome and metabolome to reveal the mechanism of microbiota-hippocampus-metabolites axis dysfunction in a mouse model of sepsis. Methods: A mouse model of sepsis was established via cecal ligation and puncture. The potential associations between the composition of the gut microbiota and metabolites in the hippocampus of mice with sepsis were investigated by combining 16S ribosomal RNA gene sequencing and ultra-high-performance liquid chromatography tandem mass spectrometry. Results: A total of 140 differential metabolites were identified in the hippocampal tissues of mice with sepsis when compared to those of control mice. These differential metabolites in mice with sepsis were not only associated with autophagy and serotonergic synapse, but also involved in the metabolism and synthesis of numerous amino acids. At the phylum level, the abundance of Bacteroidota was increased, while that of Firmicutes (Bacillota) was decreased in mice with sepsis. At the genus level, the abundance of Alistipes was increased, while that of Lachnospiraceae_NK4A136_group was decreased in mice with sepsis. The Firmicutes (Bacillota)/Bacteroidota (F/B) ratio was decreased in mice with sepsis when compared to that of control mice. Furthermore, the F/B ratio was positively correlated with 5'-methylthioadenosine, PC (18:3(9Z,12Z,15Z)/18:0) and curdione, and negatively correlated with indoxylsulfuric acid, corticosterone, kynurenine and ornithine. Conclusion: Analysis revealed a reduction in the F/B ratio in mice with sepsis, thus contributing to the disturbance of 5'-methylthioadenosine, curdione, PC (18:3(9Z,12Z,15Z)/18:0), corticosterone, ornithine, indoxylsulfuric acid and kynurenine; eventually, these changes led to hippocampus dysfunction. Our findings provide a new direction for the management of sepsis-induced hippocampus dysfunction.

4.
Carbohydr Polym ; 339: 122247, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823915

RESUMO

The escalating demand for environmentally sustainable and cost-effective adhesives in the wood processing and manufacturing sector has prompted exploration into innovative solutions. This study introduces a novel gel adhesive composed of chemically unmodified high-amylose starch (G70, with 68 % amylose content) with a minimal proportion of urea-formaldehyde (UF) (UF/starch = 1:10, w/w). This G70/UF gel demonstrates remarkable adhesive capabilities for wooden boards under both dry conditions (with a shear stress of 4.13 ± 0.12 MPa) and wet conditions (with a shear strength of 0.93 ± 0.07 MPa after 2 h of water soaking). The study unveils that the elevated amylose content in the starch, coupled with a meticulously controlled isothermal process during bonding, is crucial for these enhancements. Specifically, the robust cohesion of amylose chains expedites phase separation between starch and UF, while the isothermal process facilitates the migration and enrichment of UF molecules at the gel-board and gel-air interfaces. Lacking these mechanisms, conventional amylopectin-rich starch/UF gels (27 % amylose content) show minimal improvement. Moreover, the G70/UF gel showcases exceptional fire retardancy. In all, the G70/UF gel presents a promising alternative for plywood production, reducing reliance on unhealthy UF resin while offering satisfactory bonding resistance in diverse conditions and superior flame retardancy.

5.
Front Pharmacol ; 15: 1387409, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887546

RESUMO

Our previous study highlighted the therapeutic potential of glutathione (GSH), an intracellular thiol tripeptide ubiquitous in mammalian tissues, in mitigating hepatic and cerebral damage. Building on this premise, we posited the hypothesis that GSH could be a promising candidate for treating acute hepatic encephalopathy (AHE). To verify this conjecture, we systematically investigated the feasibility of GSH as a therapeutic agent for AHE through comprehensive pharmacokinetic, pharmacodynamic, and mechanistic studies using a thioacetamide-induced AHE rat model. Our pharmacodynamic data demonstrated that oral GSH could significantly improve behavioral scores and reduce hepatic damage of AHE rats by regulating intrahepatic ALT, AST, inflammatory factors, and homeostasis of amino acids. Additionally, oral GSH demonstrated neuroprotective effects by alleviating the accumulation of intracerebral glutamine, down-regulating glutamine synthetase, and reducing taurine exposure. Pharmacokinetic studies suggested that AHE modeling led to significant decrease in hepatic and cerebral exposure of GSH and cysteine. However, oral GSH greatly enhanced the intrahepatic and intracortical GSH and CYS in AHE rats. Given the pivotal roles of CYS and GSH in maintaining redox homeostasis, we investigated the interplay between oxidative stress and pathogenesis/treatment of AHE. Our data revealed that GSH administration significantly relieved oxidative stress levels caused by AHE modeling via down-regulating the expression of NADPH oxidase 4 (NOX4) and NF-κB P65. Importantly, our findings further suggested that GSH administration significantly regulated the excessive endoplasmic reticulum (ER) stress caused by AHE modeling through the iNOS/ATF4/Ddit3 pathway. In summary, our study uncovered that exogenous GSH could stabilize intracerebral GSH and CYS levels to act on brain oxidative and ER stress, which have great significance for revealing the therapeutic effect of GSH on AHE and promoting its further development and clinical application.

6.
J Glob Health ; 14: 04108, 2024 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-38867677

RESUMO

Background: As birth policy can affect maternal and infant health, we sought to identify whether and how the introduction of the two-child policy might have affected the prevalence of placenta previa in pregnant women in mainland China. Methods: In this update meta-analysis and systematic review, we searched PubMed, Web of Science, the Cochrane Library, Weipu, Wanfang, and the China National Knowledge Infrastructure (CNKI) databases for studies evaluating the prevalence of placenta previa in China published between the inception of each database and March 2024, with no restrictions. Two investigators independently extracted the data from each included study. We then combined the prevalence of placenta previa using random-effects models. Results: We included 128 studies in our analysis, 48 more than in our previous review. The prevalence of placenta previa among Chinese pregnant women was 1.44% (95% confidence interval (CI) = 1.32, 1.56). After the implementation of the two-child policy, the prevalence increased significantly, from 1.25% (95% CI = 1.16, 1.34) to 4.12% (95% CI = 3.33, 4.91). Conclusions: The prevalence of placenta previa increased significantly from the one-child policy period to the two-child policy period among mainland Chinese pregnant women, with varying trends across regions. This change requires the attention of health officials and timely adjustment of resource allocation policies. Registration: PROSPERO: CRD42021262309.


Assuntos
Placenta Prévia , Humanos , Gravidez , China/epidemiologia , Feminino , Placenta Prévia/epidemiologia , Prevalência , Parto Obstétrico/estatística & dados numéricos
8.
J Affect Disord ; 359: 394-402, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38806066

RESUMO

BACKGROUND: Both depression and constipation are universal disorders that seriously affect quality of life. But the phenotypic relationship and causality between depression and constipation are still unclear. METHODS: We first assessed phenotypic relationships by logistic regression analysis using large-scale data extracted from the National Health and Nutrition Examination Survey (N = 11,585). We then evaluated causality by bidirectional two-sample mendelian randomization (MR) analysis using Genome-wide association study (GWAS) data (depression: N = 807,553; constipation: N = 377,277). To investigate whether depression severity affects the causal relationship between depression and constipation, we conducted a further MR study on GWAS data of major depression (N = 480,359). RESULTS: About 11.31 % of the participants in the constipation group suffered from depression, which was significantly higher than the normal bowel group (6.09 %). The observational study showed a positive correlation between depression and constipation (OR = 1.968, 95%CI = 1.530-2.532). Besides, the risk of constipation was higher in participants with severe depression (OR = 2.294, 95%CI = 1.538-3.422) than in participants with mild depression (OR = 1.549, 95%CI = 1.242-1.932). Bidirectional MR analysis revealed an obviously causal effect of depression on constipation, but no causal effect of constipation on depression. In addition, the MR analysis also revealed a causal relationship between major depression and constipation. LIMITATION: The exact mechanism by which depression affects constipation is still unclear. CONCLUSION: This study reveals a positive correlation between depression and constipation and the causal effect of depression on constipation. Clinicians should keep the risk of constipation in mind when treating patients with depression.


Assuntos
Constipação Intestinal , Depressão , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Constipação Intestinal/epidemiologia , Constipação Intestinal/genética , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Depressão/epidemiologia , Depressão/genética , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/epidemiologia , Inquéritos Nutricionais , Idoso
9.
J Am Chem Soc ; 146(21): 14386-14390, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38747544

RESUMO

A tetragermacyclobutane-1,3-diyl was prepared and structurally characterized via the reduction of chlorogermylene-coordinated germylgermylene with potassium graphite, which represents the first all-germanium analogue of cyclobutane-1,3-diyl. Single-crystal X-ray analysis of the tetragermacyclobutane-1,3-diyl disclosed that it adopts a planar-cis structure, which is different from those reported all-silicon cyclobutane-1,3-diyls. DFT calculations revealed that both the bulky substituents on the germanium atoms and the tethering of the amido groups are important for the planar cis-configuration of 5.

10.
J Biomed Res ; : 1-14, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38808572

RESUMO

As a potential endocrine-disrupting chemical, bisphenol F (BPF) may cause nonalcoholic fatty liver disease (NAFLD)-like changes, but the mechanisms underpinning its pathogenesis as well as the intervention strategies remain poorly understood. Using the electron microscopy technology, along with LipidTOX Deep Red neutral and Bodipy 493/503 staining assays, we observed that BPF treatment elicited a striking accumulation of lipid droplets in HepG2 cells, accompanied by an increased total level of triglycerides. At the molecular level, the lipogenesis-associated mRNAs and proteins, including acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase-1, peroxisome proliferator-activated receptor gamma, and CCAAT-enhancer-binding proteins, increased significantly via the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling regulation in both in vitro and in vivo studies. Furthermore, the immunofluorescence results also showed the robust lipogenesis induced by BPF, evident in its ability to promote the translocation of sterol regulatory element-binding protein-1c from the cytoplasm to the nuclei. To investigate the intervention strategies for BPF-induced NAFLD-like changes, we demonstrated that bellidifolin, isolated and purified from Swertia chirayita, significantly attenuated BPF-induced lipid droplet deposition in HepG2 cell and NAFLD-like changes in mice by blocking the expression of lipogenesis-associated proteins. Therefore, the present study elucidates the mechanisms underlying BPF-induced lipid accumulation in HepG2 cells, while also highlighting the potential of bellidifolin to mitigate BPF-induced NAFLD-like changes.

11.
Heliyon ; 10(7): e29443, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38633623

RESUMO

Stenosis severity may escalate over the course of coronary artery disease (CAD), increasing the risk of death for the patient. Conventionally, the assessment of stenosis degree relies on invasive coronary angiography (ICA), an invasive examination unsuitable for patients in poor physical condition or those with contrast allergies and one that imposes a psychological burden on patients. Although abnormal serum N-glycan profiles have exhibited robust associations with various cardiovascular diseases, including CAD, their potential in diagnosing CAD stenosis remains to be determined. In this study, we performed a comprehensive analysis of serum N-glycome from 132 patients who underwent ICA and 27 healthy controls using MALDI-TOF-mass spectrometry. The patients who underwent ICA examination were categorized into four groups based on stenosis severity: no/mild/moderate/severe stenosis. Twenty-seven N-glycans were directly quantified, and 47 derived glycan traits were obtained. Notably, among these 74 glycan features, 18 exhibited variations across the study groups. Using a combination of least absolute shrinkage and selection operator and logistic regression analyses, we developed five diagnostic models for recognizing stenosis degree. Our results suggested that alterations in serum N-glycosylation modifications might be valuable for identifying stenosis degree and monitoring disease progression in individuals with CAD. It is expected to offer a noninvasive alternative for those who could not undergo ICA because of various reasons. However, the diagnostic potential of serum N-glycan panels as biomarkers requires multicenter, large cohort validation in the future.

12.
J Cancer Res Ther ; 20(2): 540-546, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38687923

RESUMO

PURPOSE: To retrospectively study the therapeutic effect and safety performance of the combination strategies of the computed tomography (CT)-guided microwave ablation (MWA) and percutaneous vertebroplasty (PVP) as a treatment for painful non-small cell lung cancer (NSCLC) with spinal metastases. MATERIALS AND METHODS: A retrospective review included 71 patients with 109 vertebral metastases who underwent microwave ablation combined with percutaneous vertebroplasty by the image-guided and real-time temperature monitoring. Treatment efficacy was determined by comparing visual analog scale (VAS) scores, daily morphine equivalent opioid consumption, and Oswestry Disability Index (ODI) scores before treatment and during the follow-up period. RESULTS: Technical success was achieved in all patients. The mean pre-procedure VAS score and morphine doses were 6.6 ± 1.8 (4-10) and 137.2 ± 38.7 (40-200) mg, respectively. The mean VAS scores and daily morphine doses at 24 h and 1, 4, 12, and 24 weeks postoperatively were 3.3 ± 1.9 and 73.5 ± 39.4 mg; 2.2 ± 1.5 and 40.2 ± 29.8 mg; 1.7 ± 1.2 and 31.3 ± 23.6 mg; 1.4 ± 1.1 and 27.3 ± 21.4 mg; and 1.3 ± 1.1 and 24.8 ± 21.0 mg, respectively (all P < 0.001). ODI scores significantly decreased (P < 0.05). Minor cement leakage occurred in 51 cases (46.8%), with one patient having a grade 3 neural injury. No local tumor progression was observed by follow-up imaging. CONCLUSIONS: MWA combined with PVP can significantly relieve pain and improve patients' quality of life, which implied this is an effective treatment option for painful NSCLC with spinal metastases. Additionally, its efficacy should be further verified through the mid- and long-term studies.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Micro-Ondas , Neoplasias da Coluna Vertebral , Vertebroplastia , Humanos , Masculino , Feminino , Vertebroplastia/métodos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Micro-Ondas/uso terapêutico , Neoplasias da Coluna Vertebral/secundário , Neoplasias da Coluna Vertebral/terapia , Neoplasias da Coluna Vertebral/complicações , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Terapia Combinada/métodos , Medição da Dor , Tomografia Computadorizada por Raios X , Adulto , Dor do Câncer/etiologia , Dor do Câncer/terapia , Dor do Câncer/diagnóstico , Idoso de 80 Anos ou mais , Manejo da Dor/métodos , Seguimentos
13.
J Affect Disord ; 356: 737-752, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38649105

RESUMO

The onset of depression commonly occurs in adolescence; therefore, depressive prevention and intervention are pivotal during this period. It is becoming evident that neurotransmitter imbalance and gut microbiota dysbiosis are prominent causes of depression. However, the underlying links and mechanisms remain poorly understood. In this study, with 16S ribosomal RNA gene sequencing, genus Coprococcus markedly differentiated between the healthy and unmedicated depressive adolescents. Based on this, transplantation of Coprococcus eutactus (C.e.) was found to dramatically ameliorate the chronic restraint stress (CRS) induced depression-like changes and prevent synaptic loss and glial-stimulated neuroinflammation in mice. The Ultra-high performance liquid chromatography tandem mass spectrometry analysis (UHPLC-MS/MS) further showed that neurotoxic neurotransmitters in kynurenine pathway (KP) such as 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HAA) decreased in mouse brains, mechanistically deciphering the transfer of the tryptophan metabolic pathway to serotonin metabolic signaling in the brain after C.e. treatment, which was also verified in the colon. Molecularly, blockage of KP activities mediated by C.e. was ascribed to the restraint of the limit-step enzymes responsible for kynurenine, 3-HK, and quinolinic acid generation. In the colon, C.e. treatment significantly recovered goblet cells and mucus secretion in CRS mice which may ascribe to the rebalance of the disordered gut microbiota, especially Akkermansia, Roseburia, Rikenella, Blautia, and Alloprevotella. Taken together, the current study reveals for the first time the beneficial effects and potential mechanisms of C.e. in ameliorating CRS-induced depression, unraveling the direct links between C.e. treatment and neurotransmitter rebalance, which may provide efficacious therapeutic avenues for adolescent depressive intervention.


Assuntos
Depressão , Microbioma Gastrointestinal , Neurotransmissores , Restrição Física , Estresse Psicológico , Animais , Camundongos , Microbioma Gastrointestinal/fisiologia , Estresse Psicológico/metabolismo , Estresse Psicológico/complicações , Depressão/metabolismo , Humanos , Masculino , Neurotransmissores/metabolismo , Modelos Animais de Doenças , Adolescente , Encéfalo/metabolismo , Cinurenina/metabolismo , Cinurenina/análogos & derivados
14.
Angew Chem Int Ed Engl ; 63(20): e202402881, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38433093

RESUMO

Functionalized with the Au-S bond, gold nanoflares have emerged as promising candidates for theranostics. However, the presence of intracellular abundantly biothiols compromises the conventional Au-S bond, leading to the unintended release of cargoes and associated side-effects on non-target cells. Additionally, the hypoxic microenvironment in diseased regions limits treatment efficacy, especially in photodynamic therapy. To address these challenges, high-fidelity photodynamic nanoflares constructed on Pt-coated gold nanoparticles (Au@Pt PDNF) were communicated to avoid false-positive therapeutic signals and side-effects caused by biothiol perturbation. Compared with conventional photodynamic gold nanoflares (AuNP PDNF), the Au@Pt PDNF were selectively activated by cancer biomarkers and exhibited high-fidelity phototheranostics while reducing side-effects. Furthermore, the ultrathin Pt-shell catalysis was confirmed to generate oxygen which alleviated hypoxia-related photodynamic resistance and enhanced the antitumor effect. This design might open a new venue to advance theranostics performance and is adaptable to other theranostic nanomaterials by simply adding a Pt shell.


Assuntos
Antineoplásicos , Ouro , Nanopartículas Metálicas , Platina , Nanomedicina Teranóstica , Ouro/química , Humanos , Platina/química , Nanopartículas Metálicas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Fotoquimioterapia , Sobrevivência Celular/efeitos dos fármacos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células/efeitos dos fármacos
15.
Heliyon ; 10(3): e25711, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38371985

RESUMO

Background: The potential effect of removing danger-associated molecular patterns (DAMPs) from gut lymph on reducing acute lung injury (ALI) induced by gut ischemia-reperfusion injury (GIRI) is uncertain. This study aimed to investigate whether gut lymph purification (GLP) could improve GIRI-induced acute lung injury in rats by clearing danger-associated molecular patterns. Materials and methods: Rats were divided into four groups: Sham, GIRI, GIRI + gut lymph drainage (GLD), and GIRI + GLP. After successful modeling, lung tissue samples were collected from rats for hematoxylin-eosin (HE) staining and detection of apoptotic indexes. We detected the DAMPs levels in blood and lymph samples. We observed the microstructure of AEC Ⅱ and measured the expression levels of apoptosis indexes. Results: The GIRI group showed destruction of alveolar structure, thickened alveolar walls, and inflammatory cell infiltration. This was accompanied by significantly increased levels of high mobility group protein-1 (HMGB-1) and Interleukin-6 (IL-6), while reduced levels of heat shock protein 70 (HSP 70) and Interleukin-10 (IL-10) in both lymph and serum. In contrast, the lung tissue damage in the GIRI + GLP group was significantly improved compared to the GIRI group. This was evidenced by a reduction in the expression levels of HMGB-1 and IL-6 in both lymph and serum and an increase in HSP 70 and IL-10 levels. Additionally, organelle structure of AEC II was significantly improved in the GIRI + GLP group compared to the GIRI group. Conclusions: GLP inhibits inflammation and cell apoptosis in GIRI-induced ALI by blocking the link between DAMPs and mononuclear phagocytes, reducing the severity of ALI.

16.
Environ Pollut ; 346: 123356, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38266696

RESUMO

Bisphenol F (BPF), one of the major alternatives of Bisphenol A (BPA), is becoming extensively used in industrial production with great harm to human beings and environment. Recent studies have revealed that environmental exposure is crucial to the initiation and development of depression. Thereby, the aim the present study is to ascertain the correlationship between the BPF exposure and depression occurrence. In the current study, BPF strikingly triggered depression-like changes in mice through the sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST), accompanied by the perturbation of the kynurenine (KYN) metabolic pathway along the "liver-brain" axis. Mechanistically, the neurotransmitters from the tryptophan metabolic pathway were converted to the toxic KYN pathway after BPF treatment. With the ELISA assay, it revealed that the toxic KYN metabolites, including KYN and 3-hydroxykynurenine (3-HK), were strikingly increased in the mouse brains which was ascribed to the enhanced expression of the rate-limiting enzymes Indoleamine 2,3-dioxygenase (IDO1) and Kynurenine 3-monooxygenase (KMO) respectively. Interestingly, the increased brain KYN induced by BPF was also validated partially from the periphery, since the ELISA and western blotting results indicated the significantly increased KYN in the serum and L-type amino acid transporter 1 (LAT1) in the brain, the key transporter responsible for KYN and 3-HK crossing the blood-brain barrier. Intriguingly, the liver-derived KYN metabolic pathway was the important source of the peripheral KYN and 3-HK, as BPF substantially enhanced hepatic IDO1, Tryptophan, 2, 3-dioxygenase (TDO2), and KMO levels indicated by western blotting. This study is the first to delineate previously unrecognized BPF-induced depression by regulating the KYN metabolic pathway along the "liver-brain" axis; therefore, targeting LAT1 or hepatic KYN signaling may provide a potentially unique therapeutic intervention in BPF-induced depression.


Assuntos
Compostos Benzidrílicos , Cinurenina , Fenóis , Triptofano , Humanos , Camundongos , Animais , Cinurenina/metabolismo , Triptofano/metabolismo , Depressão/induzido quimicamente , Encéfalo/metabolismo , Fígado/metabolismo , Redes e Vias Metabólicas
17.
Commun Biol ; 7(1): 32, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182876

RESUMO

Preeclampsia is a multifactorial and heterogeneous complication of pregnancy. Here, we utilize single-cell RNA sequencing to dissect the involvement of circulating immune cells in preeclampsia. Our findings reveal downregulation of immune response in lymphocyte subsets in preeclampsia, such as reduction in natural killer cells and cytotoxic genes expression, and expansion of regulatory T cells. But the activation of naïve T cell and monocyte subsets, as well as increased MHC-II-mediated pathway in antigen-presenting cells were still observed in preeclampsia. Notably, we identified key monocyte subsets in preeclampsia, with significantly increased expression of angiogenesis pathways and pro-inflammatory S100 family genes in VCAN+ monocytes and IFN+ non-classical monocytes. Furthermore, four cell-type-specific machine-learning models have been developed to identify potential diagnostic indicators of preeclampsia. Collectively, our study demonstrates transcriptomic alternations of circulating immune cells and identifies immune components that could be involved in pathophysiology of preeclampsia.


Assuntos
Pré-Eclâmpsia , Feminino , Gravidez , Humanos , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/genética , Células Apresentadoras de Antígenos , Aprendizado de Máquina , Transcriptoma , Análise de Sequência de RNA
18.
J Sep Sci ; 47(2): e2300784, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38286734

RESUMO

Charged aerosol detection, increasingly recognized for quantifying pharmaceutical compounds with weak ultraviolet absorption, is a universal detection technique for high-performance liquid chromatography (HPLC). Charged aerosol detection shows a non-linear response with increasing analyte concentration over a wide range, limiting its versatility in various analytical applications. In this work, a co-optimization strategy for power function value (PFV) and power laws was proposed and applied to broaden the linear range of the standard curve of saccharides in Qishen Yiqi dripping pills using the HPLC-charged aerosol detection (HPLC-CAD) method. Power function values for all analytes were optimized based on empirical models. Subsequently, the optimum power laws were investigated based on a preferred PFV. Additionally, various regression equations were evaluated to ensure the accuracy and precision of the results. With the optimized PFV and power law, the ordinary least squares model demonstrated a satisfactory fit. The optimal PFVs and power laws expanded the standard curve's linear range by 2.7 times compared to default settings, reducing model uncertainty. This paper presents a vital method for developing a multi-component quantitative HPLC-CAD approach without external data transformation outside the provided software, especially suitable for analytical applications of traditional Chinese medicine with significant quality differences.


Assuntos
Medicamentos de Ervas Chinesas , Aerossóis/análise , Carboidratos , Cromatografia Líquida de Alta Pressão/métodos
19.
Macromol Rapid Commun ; 45(4): e2300557, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37880914

RESUMO

Eutectogels are gaining attention in flexible device applications for their superior ionic conductivity, stability, biocompatibility, and cost-effectiveness. However, most existing eutectogels suffer from low strength and toughness. Herein, ultra-tough and highly stretchable polyacrylamide (PAM) eutectogels featuring a dual-crosslinked network comprising chemical cross-linking and physical cross-linking facilitated by metal coordination bonds and hydrogen bonds are developed. This is achieved through a controlled strategy involving polymerization of acrylamide in a coordinated metal salt-type deep eutectic solvent (DES) combined with a non-coordinated choline chloride (ChCl)-type DES mixture. By varying the molar ratio of these two types of DES, exceptional and adjustable mechanical properties of the resulting eutectogel are achieved, including a high tensile strength ranging from 2.9 to 8.2 MPa and elongation at break ranging from 1725 to 747%, at a 70 wt% DES content. Furthermore, the reversible non-covalent crosslinking in these eutectogels enables self-recovery and self-healing capabilities of eutectogels. The prepared eutectogels also exhibit outstanding ionic conductivity (3.56 mS cm-1 ), making them well-suited for use as strain sensors in human motion detection. The toughening strategy is universally effective for creating tough eutectogels using coordinated metal salt-type DES with various metal ions, as well as a diverse range of coordinatable polymers.


Assuntos
Acrilamida , Solventes Eutéticos Profundos , Humanos , Colina , Condutividade Elétrica , Ligação de Hidrogênio , Cloreto de Sódio
20.
Int J Biol Macromol ; 254(Pt 2): 127938, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37944723

RESUMO

While high-amylose starch (HAS) possesses advantageous properties such as high resistant starch content and favorable mechanical attributes, its gelatinization constraints have limited its applicability. This study enhances its versatility by focusing on pre-gelatinized (PG) HAS with exceptional rehydratability, achieved by disorganizing native HAS granules (with amylose contents of 55 % and 68 %, respectively) using a 33 % CaCl2 solution, followed by water-ethanol precipitation and freeze-drying. The resulting PG-HAS exhibited elevated amylose content (61 % and 75 %) with minimal changes in amylose molecular weight. PG-HAS displayed superior water-absorption index (WAI) and water-soluble index (WSI) compared to native HAS, further improved by 2 % CaCl2 solution incorporation. Furthermore, composite films were prepared by mixing PG-HAS with PVA at a 6:4 (w/w) ratio. The PG-G50 (61 % amylose content)/PVA composite film exhibited remarkable elongation (131.1 ± 5.4 %), nearly three times that of a normal corn starch (NCS, with 27 % amylose)/PVA film, attributed to improved starch dispersity and higher amylose content. Nonetheless, the PG-G70 (75 % amylose content)/PVA film at the same ratio showed lower elongation (54.7 ± 8.0 %), potentially due to strong cohesive forces between amylose chains that impede starch-PVA interactions. Moreover, the PG-HAS/PVA composite films, enriched with antibacterial agents, demonstrated effective antibacterial properties with a gradual and sustained release of active compounds. Notably, the PG-G50/PVA/tannic acid (TA) film effectively preserved fresh apple slices by inhibiting bacteria growth and preventing browning. These findings underscore the excellent rehydration of PG-HAS and its potential as an inner packaging material for irregularly shaped foods, such as sliced fruits or meats, due to its nontoxic nature, softness and flexibility, which allows the film to maintain close contact with food surfaces.


Assuntos
Anti-Infecciosos , Amido , Amilose , Frutas , Cloreto de Cálcio , Antibacterianos/farmacologia , Água
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