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1.
BMC Genomics ; 25(1): 338, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575927

RESUMO

BACKGROUND: Due to rising costs, water shortages, and labour shortages, farmers across the globe now prefer a direct seeding approach. However, submergence stress remains a major bottleneck limiting the success of this approach in rice cultivation. The merger of accumulated rice genetic resources provides an opportunity to detect key genomic loci and candidate genes that influence the flooding tolerance of rice. RESULTS: In the present study, a whole-genome meta-analysis was conducted on 120 quantitative trait loci (QTL) obtained from 16 independent QTL studies reported from 2004 to 2023. These QTL were confined to 18 meta-QTL (MQTL), and ten MQTL were successfully validated by independent genome-wide association studies from diverse natural populations. The mean confidence interval (CI) of the identified MQTL was 3.44 times narrower than the mean CI of the initial QTL. Moreover, four core MQTL loci with genetic distance less than 2 cM were obtained. By combining differentially expressed genes (DEG) from two transcriptome datasets with 858 candidate genes identified in the core MQTL regions, we found 38 common differentially expressed candidate genes (DECGs). In silico expression analysis of these DECGs led to the identification of 21 genes with high expression in embryo and coleoptile under submerged conditions. These DECGs encode proteins with known functions involved in submergence tolerance including WRKY, F-box, zinc fingers, glycosyltransferase, protein kinase, cytochrome P450, PP2C, hypoxia-responsive family, and DUF domain. By haplotype analysis, the 21 DECGs demonstrated distinct genetic differentiation and substantial genetic distance mainly between indica and japonica subspecies. Further, the MQTL7.1 was successfully validated using flanked marker S2329 on a set of genotypes with phenotypic variation. CONCLUSION: This study provides a new perspective on understanding the genetic basis of submergence tolerance in rice. The identified MQTL and novel candidate genes lay the foundation for marker-assisted breeding/engineering of flooding-tolerant cultivars conducive to direct seeding.


Assuntos
Oryza , Mapeamento Cromossômico , Oryza/genética , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Genômica , Perfilação da Expressão Gênica
2.
World J Gastroenterol ; 30(9): 1177-1188, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577193

RESUMO

BACKGROUND: Acute decompensation (AD) of cirrhosis is associated with high short-term mortality, mainly due to the development of acute-on-chronic liver failure (ACLF). Thus, there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is released from activated innate immune cells and correlated with various inflammatory processes. AIM: To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis. METHODS: A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort (n = 309) and validation cohort (n = 133). Demographic and clinical data were collected, and serum sTREM-1 was measured at admission. All enrolled patients were followed-up for at least 1 year. RESULTS: In patients with AD and cirrhosis, serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver, coagulation, cerebral and kidney failure. A new prognostic model of AD (P-AD) incorporating sTREM-1, blood urea nitrogen (BUN), total bilirubin (TBil), international normalized ratio (INR) and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease (MELD), MELD-sodium (MELD-Na), chronic liver failure-consortium (CLIF-C) ACLF and CLIF-C AD scores. Additionally, sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up. The ACLF risk score incorporating serum sTREM-1, BUN, INR, TBil and aspartate aminotransferase levels was established and significantly superior to MELD, MELD-Na, CLIF-C ACLF, CLIF-C AD and P-AD in predicting risk of ACLF development. CONCLUSION: Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.


Assuntos
Insuficiência Hepática Crônica Agudizada , Doença Hepática Terminal , Humanos , Insuficiência Hepática Crônica Agudizada/etiologia , Insuficiência Hepática Crônica Agudizada/complicações , Receptor Gatilho 1 Expresso em Células Mieloides , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Biomarcadores
3.
Artigo em Inglês | MEDLINE | ID: mdl-38562440

RESUMO

Objective: To comparison of the application of Vibrating Mesh Nebulizer and Jet Nebulizer in chronic obstructive pulmonary disease (COPD). Research Methods: This systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statements. The primary outcome measures analyzed included: The amount of inhaler in the urine sample at 30 minutes after inhalation therapy (USAL0.5), The total amount of inhaler in urine sample within 24 hours (USAL24), Aerosol emitted, Forced expiratory volume in 1 second (FEV1), Forced vital capacity (FVC). Results: Ten studies were included with a total of 314 study participants, including 157 subjects in the VMN group and 157 subjects in the JN group. The data analysis results of USAL0.5, MD (1.88 [95% CI, 0.95 to 2.81], P = 0.000), showed a statistically significant difference. USAL24, MD (1.61 [95% CI, 1.14 to 2.09], P = 0.000), showed a statistically significant difference. The results of aerosol emitted showed a statistically significant difference in MD (3.44 [95% CI, 2.84 to 4.04], P = 0.000). The results of FEV1 showed MD (0.05 [95% CI, -0.24 to 0.35], P=0.716), the results were not statistically significant. The results of FVC showed MD (0.11 [95% CI, -0.18 to 0.41], P=0.459), the results were not statistically significant. It suggests that VMN is better than JN and provides higher aerosols, but there is no difference in improving lung function between them. Conclusion: VMN is significantly better than JN in terms of drug delivery and utilization in the treatment of patients with COPD. However, in the future use of nebulizers, it is important to select a matching nebulizer based on a combination of factors such as mechanism of action of the nebulizer, disease type and comorbidities, ventilation strategies and modes, drug formulations, as well as cost-effectiveness, in order to achieve the ideal treatment of COPD.


Assuntos
Broncodilatadores , Doença Pulmonar Obstrutiva Crônica , Humanos , Administração por Inalação , Albuterol , Broncodilatadores/efeitos adversos , Sistemas de Liberação de Medicamentos , Desenho de Equipamento , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Aerossóis e Gotículas Respiratórios
4.
Cell Biol Int ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436106

RESUMO

Mitochondrial dysfunction and myocardial remodeling have been reported to be the main underlying molecular mechanisms of doxorubicin-induced cardiotoxicity. SIRT6 is a nicotinamide adenine dinucleotide-dependent enzyme that plays a vital role in cardiac protection against various stresses. Moreover, previous studies have demonstrated that FSTL1 could alleviate doxorubicin-induced cardiotoxicity by inhibiting autophagy. The present study investigated the probable mechanisms of FSTL1 on doxorubicin-induced cardiotoxicity in vivo and in vitro. We confirmed that FSTL1 exerted a pivotal protective role on cardiac tissue in vivo and on doxorubicin-induced cell injury in vitro. Furthermore, FSTL1 can alleviate doxorubicin-induced mitochondrial dysfunction by inhibiting autophagy and apoptosis. Further studies demonstrated that FSTL1 can activate SIRT6 signaling by restoring the SIRT6 protein expression in doxorubicin-induced myocardial injury. SIRT6 activation elevated the protein expression of Nrf2 in doxorubicin-induced H9C2 injury. Treatment with the Nrf2 inhibitor ML385 partially antagonized the cardioprotective role of SIRT6 on doxorubicin-induced autophagy or apoptosis. These results suggested that the protective mechanism of FSTL1 on doxorubicin-induced cardiotoxicity may be related with the inhibition of autophagy and apoptosis, partly through the activation of SIRT6/Nrf2.

5.
JMIR Public Health Surveill ; 10: e55327, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483459

RESUMO

BACKGROUND: Asthma has become one of the most common chronic conditions worldwide, especially among children. Recent findings show that the prevalence of childhood asthma has increased by 12.6% over the past 30 years, with >262 million people currently affected globally. The reasons for the growing asthma epidemic remain complex and multifactorial. OBJECTIVE: This study aims to provide an up-to-date analysis of the changing global and regional asthma prevalence, mortality, disability, and risk factors among children aged <20 years by leveraging the latest data from the Global Burden of Disease Study 2019. Findings from this study can help inform priority areas for intervention to alleviate the rising burden of childhood asthma globally. METHODS: The study used data from the Global Burden of Disease Study 2019, concentrating on children aged 0 to 14 years with asthma. We conducted an in-depth analysis of asthma, including its age-standardized prevalence, incidence, mortality, and disability-adjusted life years (DALYs), across diverse demographics, such as region, age, sex, and sociodemographic index, spanning 1990 to 2019. We also projected the future burden of the disease. RESULTS: Overall, in the Western Pacific Region, the age-standardized prevalence rate of asthma among children increased slightly, from 3898.4 cases per 100,000 people in 1990 to 3924 per 100,000 in 2019. The age-standardized incidence rate of asthma also increased slightly, from 979.2 to 994.9 per 100,000. In contrast, the age-standardized death rate of asthma decreased from 0.9 to 0.4 per 100,000 and the age-standardized DALY rate decreased from 234.9 to 189.7 per 100,000. At the country level, Japan experienced a considerable decrease in the age-standardized prevalence rate of asthma among children, from 6669.1 per 100,000 in 1990 to 5071.5 per 100,000 in 2019. Regarding DALYs, Japan exhibited a notable reduction, from 300.6 to 207.6 per 100,000. Malaysia also experienced a DALY rate reduction, from 188.4 to 163.3 per 100,000 between 1990 and 2019. We project that the burden of disease in countries other than Japan and the Philippines will remain relatively stable up to 2045. CONCLUSIONS: The study indicates an increase in the prevalence and incidence of pediatric asthma, coupled with a decrease in mortality and DALYs in the Western Pacific Region between 1990 and 2019. These intricate phenomena appear to result from a combination of lifestyle shifts, environmental influences, and barriers to health care access. The findings highlight that nations such as Japan have achieved notable success in managing asthma. Overall, the study identified areas of improvement in view of persistent disease burden, underscoring the need for comprehensive collaborative efforts to mitigate the impact of pediatric asthma throughout the region.


Assuntos
Asma , Epidemias , Criança , Humanos , Asma/epidemiologia , Efeitos Psicossociais da Doença , Acesso aos Serviços de Saúde , Japão , Lactente , Pré-Escolar , Adolescente
6.
Proc Natl Acad Sci U S A ; 121(13): e2313239121, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38498710

RESUMO

High-entropy alloy nanoparticles (HEANs) possessing regulated defect structure and electron interaction exhibit a guideline for constructing multifunctional catalysts. However, the microstructure-activity relationship between active sites of HEANs for multifunctional electrocatalysts is rarely reported. In this work, HEANs distributed on multi-walled carbon nanotubes (HEAN/CNT) are prepared by Joule heating as an example to explain the mechanism of trifunctional electrocatalysis for oxygen reduction, oxygen evolution, and hydrogen evolution reaction. HEAN/CNT excels with unmatched stability, maintaining a 0.8V voltage window for 220 h in zinc-air batteries. Even after 20 h of water electrolysis, its performance remains undiminished, highlighting exceptional endurance and reliability. Moreover, the intrinsic characteristics of the defect structure and electron interaction for HEAN/CNT are investigated in detail. The electrocatalytic mechanism of trifunctional electrocatalysis of HEAN/CNT under different conditions is identified by in situ monitoring and theoretical calculation. Meanwhile, the electron interaction and adaptive regulation of active sites in the trifunctional electrocatalysis of HEANs were further verified by density functional theory. These findings could provide unique ideas for designing inexpensive multifunctional high-entropy electrocatalysts.

7.
Transl Psychiatry ; 14(1): 151, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504095

RESUMO

Integrating CYP2D6 genotyping and therapeutic drug monitoring (TDM) is crucial for guiding individualized atomoxetine therapy in children with attention-deficit/hyperactivity disorder (ADHD). The aim of this retrospective study was (1) to investigate the link between the efficacy and tolerability of atomoxetine in children with ADHD and plasma atomoxetine concentrations based on their CYP2D6 genotypes; (2) to offer TDM reference range recommendations for atomoxetine based on the CYP2D6 genotypes of children receiving different dosage regimens. This retrospective study covered children and adolescents with ADHD between the ages of 6 and <18, who visited the psychological and behavioral clinic of Children's Hospital of Nanjing Medical University from June 1, 2021, to January 31, 2023. The demographic information and laboratory examination data, including CYP2D6 genotype tests and routine TDM of atomoxetine were obtained from the hospital information system. We used univariate analysis, Mann-Whitney U nonparametric test, Kruskal-Wallis test, and the receiver operating characteristic (ROC) curve to investigate outcomes of interest. 515 plasma atomoxetine concentrations of 385 children (325 boys and 60 girls) with ADHD between 6 and 16 years of age were included for statistical analysis in this study. Based on genotyping results, >60% of enrolled children belonged to the CYP2D6 extensive metabolizer (EM), while <40% fell into the intermediate metabolizer (IM). CYP2D6 IMs exhibited higher dose-corrected plasma atomoxetine concentrations by 1.4-2.2 folds than those CYP2D6 EMs. Moreover, CYP2D6 IMs exhibited a higher response rate compare to EMs (93.55% vs 85.71%, P = 0.0132), with higher peak plasma atomoxetine concentrations by 1.67 times than those of EMs. Further ROC analysis revealed that individuals under once daily in the morning (q.m.) dosing regimen exhibited a more effective response to atomoxetine when their levels were ≥ 268 ng/mL (AUC = 0.710, P < 0.001). In addition, CYP2D6 IMs receiving q.m. dosing of atomoxetine were more likely to experience adverse reactions in the central nervous system and gastrointestinal system when plasma atomoxetine concentrations reach 465 and 509 ng/mL, respectively. The findings in this study provided promising treatment strategy for Chinese children with ADHD based on their CYP2D6 genotypes and plasma atomoxetine concentration monitoring. A peak plasma atomoxetine concentration higher than 268 ng/mL might be requisite for q.m. dosing. Assuredly, to validate and reinforce these initial findings, it is necessary to collect further data in controlled studies with a larger sample size.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Adolescente , Criança , Feminino , Humanos , Masculino , Inibidores da Captação Adrenérgica/efeitos adversos , Cloridrato de Atomoxetina/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/genética , Citocromo P-450 CYP2D6/genética , Monitoramento de Medicamentos , Genótipo , Propilaminas/efeitos adversos , Estudos Retrospectivos , Lactente , Pré-Escolar
8.
J Control Release ; 368: 329-343, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38431094

RESUMO

Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by excessive inflammation in the joints. Glucocorticoid drugs are used clinically to manage RA symptoms, while their dosage and duration need to be tightly controlled due to severe adverse effects. Using dexamethasone (DEX) as a model drug, we explored here whether peptide-guided delivery could increase the safety and therapeutic index of glucocorticoids for RA treatment. Using multiple murine RA models such as collagen-induced arthritis (CIA), we found that CRV, a macrophage-targeting peptide, can selectively home to the inflammatory synovium of RA joints upon intravenous injection. The expression of the CRV receptor, retinoid X receptor beta (RXRB), was also elevated in the inflammatory synovium, likely being the basis of CRV targeting. CRV-conjugated DEX increased the accumulation of DEX in the inflamed synovium but not in healthy organs of CIA mice. Therefore, CRV-DEX demonstrated a stronger efficacy to suppress synovial inflammation and alleviate cartilage/bone destruction. Meanwhile, CRV conjugation reduced immune-related adverse effects of DEX even after a long-term use. Last, we found that RXRB expression was significantly elevated in human patient samples, demonstrating the potential of clinical translation. Taken together, we provide a novel, peptide-targeted strategy to improve the therapeutic efficacy and safety of glucocorticoids for RA treatment.


Assuntos
Artrite Experimental , Artrite Reumatoide , Humanos , Camundongos , Animais , Glucocorticoides/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Inflamação , Artrite Experimental/tratamento farmacológico , Peptídeos/uso terapêutico , Índice Terapêutico
9.
Heliyon ; 10(5): e26200, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38495146

RESUMO

Postoperative delirium (POD) is a severe postoperative complication characterized by delirium-like symptoms. So far, no effective preventable strategy for POD prevention has been identified. Reports show that the consumption of green tea polyphenols (GTP) is associated with better cognitive function by modulating the composition of gut microbiota. Whether GTP also play a role in alleviating POD through gut microbiota is unknown. Herein, we studied the effect of prolonged (eight weeks) GTP intake on postoperative delirium in C57BL/6 mice with laparotomies under isoflurane anesthesia (anesthesia/surgery). We subsequently investigated anesthesia/surgery caused behavioral changes and increased the expression of malondialdehyde (MAD), an oxidative stress marker, and the activities of superoxide dismutase (SOD), an antioxidant marker, in the mice at 6 h after anesthesia/surgery. However, GTP administration reversed these changes and alleviated anesthesia/surgery-induced decrease in the abundance of gut bacterial genera, Roseburia. Further, fecal microbiota transplant demonstrated that compared with mice in the control group, treatment of C57BL/6 mice with feces from GTP-treated mice had a slight effect on the behavioral changes of mice. These data suggest that daily consumption of GTP could protect against anesthesia/surgery-induced behavioral changes, which is closely associated with gut microbiota modification by GTP.

10.
Huan Jing Ke Xue ; 45(3): 1525-1538, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471867

RESUMO

Shallow groundwater is the main source of water for living and industrial and agricultural production in Anqing City, which is an important basic guarantee to maintain the sustainable development of the social economy and regional ecological environment. In order to further study the water chemical characteristics and controlling factors of shallow groundwater in Anqing City, 196 groups of shallow groundwater samples were collected. A Piper diagram graph, Gibbs chart, ion ratio, and mathematical statistics were comprehensively used to study the water chemical characteristics and controlling factors of groundwater in Anqing City, and the contribution of different sources to the water chemical components of groundwater was quantitatively evaluated. The results showed that the shallow groundwater in Anqing City was weakly alkaline, with pH values ranging from 5.84 to 8.38, with an average value of 7.21. The TDS ranged from 47 to 1 620 mg·L-1, with an average of 324.21 mg·L-1. HCO3- and Ca2+ were the main anions, and the water chemical type was HCO3-Ca type. The chemical components of groundwater were affected by rock weathering leaching, cation alternating adsorption, mineral dissolution and precipitation, and human activities. Ca2+, Mg2+, and HCO3- were mainly derived from the weathering dissolution of carbonate and silicate; Na+, Cl-, and SO42- were affected by industrial activities and domestic sewage discharge; and K+ and NO3- were affected by agricultural activities. The APCS-MLR receptor model analysis further revealed that the chemical components of groundwater were mainly geological factors, industrial factors, agricultural factors, and unknown sources, and their contribution rates were 45.35%, 14.19%, 25.38%, and 15.08%, respectively. Geological factors were important sources of hydrochemical components of shallow groundwater, and human activities aggravated the evolution of groundwater hydrochemistry.

11.
Huan Jing Ke Xue ; 45(2): 792-801, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471918

RESUMO

The northern plain of Henan in the lower reaches of the Yellow River is an area where the Yellow River is frequently diverted. The shallow groundwater quality in this area is poor, and many types of components have been found to be exceeding the limit value; however, the contribution of various environmental factors to water quality needs to be further quantified. In order to clarify the genesis of water quality of shallow groundwater in the study area, 330 groups of shallow groundwater samples were collected via a regional water quality survey. The evolution of shallow groundwater quality in the Yellow River diversion area of northern Henan was revealed using the principal component-absolute principal component score-multiple linear regression (PCA-APCS-MLR) model. The results showed that the components with a shallow groundwater excess rate greater than 10% in descending order were manganese, iron, total hardness, total dissolved solids, sodium, fluoride, arsenic, chloride ions, sulfate, and ammonium. In particular, the excess rate of manganese reached 76%. The four factors of dissolution enrichment, native origin of soil, redox conditions, and agricultural activities were identified as the main reasons for poor groundwater quality, which accounted for 71.24% of the cumulative interpretation rate of variance. In addition, the recharge from the surface water also influenced the groundwater quality. The effects of dissolution between the water and aquifer matrix and redox condition in the aquifer of the Yellow River dried-riverway like Xinxiang were significantly enhanced, resulting in the increasing concentration of iron, arsenic, total hardness, TDS, and other components in groundwater. Fluoride enrichment was caused by dissolution enrichment, the origin of the soil, and lateral replenishment of the Yellow River. Groundwater with high manganese concentration was widely affected by the soil matrix. Nitrate pollution of the groundwater was caused by the extensive use of chemical fertilizers in agricultural activities in individual areas.

12.
Materials (Basel) ; 17(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38473624

RESUMO

As a thermal interface material, diamond/GaInSn composites have wide-ranging application prospects in the thermal management of chips. However, studies on systematic reliability that can guide the practical application of diamond/GaInSn in the high-temperature, high-temperature impact, or high-humidity service environments that are faced by chips remain lacking. In this study, the performance evolution of diamond/GaInSn was studied under high-temperature storage (150 °C), high- and low-temperature cycling (-50 °C to 125 °C), and high temperature and high humidity (85 °C and 85% humidity). The experimental results reveal the failure mechanism of semi-solid composites during high temperature oxidation. It is revealed that core oxidation is the key to the degradation of liquid metal composites' properties under high-temperature storage and high- and low-temperature cycling conditions. Under the conditions of high temperature and high humidity, the failure of Ga-based liquid metal and its composite materials is significant. Therefore, the material should avoid high-temperature and high-humidity environments.

13.
Chemistry ; : e202400360, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376356

RESUMO

Owing to well-defined structure as well as easy synthesis and modification, metal-organic frameworks (MOFs) have emerged as promising catalysts for tandem reactions. In this article, we aim to summarize the development of multifunctional MOFs, including mixed metal MOFs, MOFs that are synergistically catalyzed by metal nodes and organic linkers, MOFs loaded with metal nanoparticles, etc, as heterogenous catalysts for tandem reactions over the past five years. This concept briefly discusses on present challenges, future trends, and prospects of multifunctional MOFs catalysts in tandem reactions.

14.
J Cancer ; 15(5): 1462-1486, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356723

RESUMO

Tumor metastasis is a key factor affecting the life of patients with malignant tumors. For the past hundred years, scientists have focused on how to kill cancer cells and inhibit their metastasis in vivo, but few breakthroughs have been made. Here we hypothesized a novel mode for cancer metastasis. We show that the phagocytosis of apoptotic tumor cells by macrophages leads to their polarization into the M2 phenotype, and that the expression of stem cell related as well as drug resistance related genes was induced. Therefore, it appears that M2 macrophages have "defected" and have been transformed into the initial "metastatic cancer cells", and thus are the source, at least in part, of the distal tissue tumor metastasis. This assumption is supported by the presence of fused cells with characteristics of both macrophage and tumor cell observed in the peripheral blood and ascites of patients with ovarian cancer. By eliminating the expression of CD206 in M2 macrophages using siRNA, we show that the growth and metastasis of tumors was suppressed using both in vitro cell line and with experimental in vivo mouse models. In summary, we show that M2 macrophages in the blood circulation underwent a "change of loyalty" to become "cancer cells" that transformed into distal tissue metastasis, which could be suppressed by the knockdown of CD206 expression.

15.
Molecules ; 29(4)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38398662

RESUMO

The microglia, displaying diverse phenotypes, play a significant regulatory role in the development, progression, and prognosis of Parkinson's disease. Research has established that glycolytic reprogramming serves as a critical regulator of inflammation initiation in pro-inflammatory macrophages. Furthermore, the modulation of glycolytic reprogramming has the potential to reverse the polarized state of these macrophages. Previous studies have shown that Levistilide A (LA), a phthalide component derived from Angelica sinensis, possesses a range of pharmacological effects, including anti-inflammatory, antioxidant, and neuroprotective properties. In our study, we have examined the impact of LA on inflammatory cytokines and glucose metabolism in microglia induced by lipopolysaccharide (LPS). Furthermore, we explored the effects of LA on the AMPK/mTOR pathway and assessed its neuroprotective potential both in vitro and in vivo. The findings revealed that LA notably diminished the expression of M1 pro-inflammatory factors induced by LPS in microglia, while leaving M2 anti-inflammatory factor expression unaltered. Additionally, it reduced ROS production and suppressed IκB-α phosphorylation levels as well as NF-κB p65 nuclear translocation. Notably, LA exhibited the ability to reverse microglial glucose metabolism reprogramming and modulate the phosphorylation levels of AMPK/mTOR. In vivo experiments further corroborated these findings, demonstrating that LA mitigated the death of TH-positive dopaminergic neurons and reduced microglia activation in the ventral SNpc brain region of the midbrain and the striatum. In summary, LA exhibited neuroprotective benefits by modulating the polarization state of microglia and altering glucose metabolism, highlighting its therapeutic potential.


Assuntos
Compostos Heterocíclicos de Anel em Ponte , Fármacos Neuroprotetores , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , NF-kappa B/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Microglia , Lipopolissacarídeos/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Anti-Inflamatórios/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Glucose/metabolismo
16.
Zhongguo Zhong Yao Za Zhi ; 49(2): 518-533, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403327

RESUMO

The efficacy and safety of different Chinese patent medicines in the treatment of coronary heart disease complicated with heart failure were evaluated by network Meta-analysis. The randomized controlled trial(RCT) of Chinese patent medicines for coronary heart disease complicated with heart failure was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library with the time interval from inception to July 5, 2023. The quality of the included RCT was evaluated by the Cochrane's risk of bias assessment tool, and a network Meta-analysis was performed in Stata 16.0. Finally, a total of 82 RCTs were included, involving 9 298 patients and 11 Chinese patent medicines. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of improving the clinical response rate, the top three interventions were Qishen Yiqi Dripping Pills + conventional western medicine, Zhenyuan Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(2) In terms of increasing left ventricular ejection fraction(LVEF), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Compound Danshen Dripping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(3) In terms of reducing left ventricular end-diastolic diameter(LVEDD), the top three interventions were Shexiang Tongxin Dripping Pills + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(4) In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Qi-shen Yiqi Dripping Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(5) In terms of reducing hyper-sensitive C-reactive protein(hs-CRP), the top three interventions were Naoxintong Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(6) In terms of increasing the distance of the six-minute walking trail(6MWT), the top three interventions were Zhen-yuan Capsules + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Qishen Yiqi Dripping Pills + conventional western medicine. The results showed that Chinese patent medicines combined with conventional western medicine can effectively improve the clinical response rate, LVEF, and 6MWT and reduce LVEDD, NT-proBNP, and hs-CRP. However, due to the overall low quality of the articles included and the few articles of some Chinese patent medicines, direct comparison between diffe-rent Chinese patent medicines remains to be carried out and the results need to be further verified.


Assuntos
Doença das Coronárias , Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Humanos , Metanálise em Rede , Medicamentos sem Prescrição/uso terapêutico , Proteína C-Reativa , Volume Sistólico , Função Ventricular Esquerda , Medicamentos de Ervas Chinesas/uso terapêutico , Doença das Coronárias/complicações , Doença das Coronárias/tratamento farmacológico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico
17.
PLoS One ; 19(2): e0299331, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38394164

RESUMO

Drug addiction can cause severe damage to the human brain, leading to significant problems in cognitive processing, such as irritability, speech distortions, and exaggeration of negative stimuli. Speech plays a fundamental role in social interaction, including both the production and perception. The ability to perceive communicative functions conveyed through speech is crucial for successful interpersonal communication and the maintaining good social relationships. However, due to the limited number of previous studies, it remains unclear whether the cognitive disorder caused by drug addiction affects the perception of communicative function conveyed in Mandarin speech. To address this question, we conducted a perception experiment involving sixty male participants, including 25 heroin addicts and 35 healthy controls. The experiment aimed to examine the perception of three communicative functions (i.e., statement, interrogative, and imperative) under three background noise conditions (i.e., no noise, SNR [Signal to Noise Ratio] = 10, and SNR = 0). Eight target sentences were first recorded by two native Mandarin speakers for each of the three communicative functions. Each half was then combined with Gaussian White Noise under two background noise conditions (i.e., SNR = 10 and SNR = 0). Finally, 48 speech stimuli were included in the experiment with four options provided for perceptual judgment. The results showed that, under the three noise conditions, the average perceptual accuracies of the three communicative functions were 80.66% and 38% for the control group and the heroin addicts, respectively. Significant differences were found in the perception of the three communicative functions between the control group and the heroin addicts under the three noise conditions, except for the recognition of imperative under strong noise condition (i.e., SNR = 0). Moreover, heroin addicts showed good accuracy (around 50%) in recognizing imperative and poor accuracy (i.e., lower than the chance level) in recognizing interrogative. This paper not only fills the research gap in the perception of communicative functions in Mandarin speech among drug addicts but also enhances the understanding of the effects of drugs on speech perception and provides a foundation for the speech rehabilitation of drug addicts.


Assuntos
Percepção da Fala , Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Fala , Heroína , China
18.
Eur J Med Chem ; 267: 116223, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38342013

RESUMO

Acute lung injury (ALI) is a clinically high mortality disease, which has not yet been effectively treated. The development of anti-ALI drugs is imminent. ALI can be effectively treated by inhibiting the inflammatory cascade and reducing the inflammatory response in the lung. Forsythia suspense is a common Chinese herbal medicine with significant anti-inflammatory activity. Using forsythin as the parent, 27 Forsythin derivatives were designed and synthesized, and the anti-AIL activity of these compounds was evaluated. Among them, compound B5 has the best activity to inhibit the release of IL-6, and the inhibition rate reaches 91.79% at 25 µM, which was 7.5 times that of the parent forsythin. In addition, most of the compounds have no significant cytotoxicity in vitro. Further studies showed that compound B5 had a concentration-dependent inhibitory effect on NO, IL-6 and TNF-α. And the IC50 values of compound B5 for NO and IL-6 are 10.88 µM and 4.93 µM, respectively. We also found that B5 could significantly inhibit the expression of some immune-related cytotoxic factors, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, B5 inhibits NF-κB/MAPK signaling pathway. In vivo experiments showed that B5 could alleviate lung inflammation in LPS-induced ALI mice and inhibit IL-6, TNF-α, COX-2 and iNOS. In summary, B5 has anti-inflammatory effects and alleviates ALI by regulating inflammatory mediators and inhibiting MAPK and NF-κB signaling pathways.


Assuntos
Lesão Pulmonar Aguda , Glucosídeos , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Ciclo-Oxigenase 2/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Lipopolissacarídeos/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo
19.
Int Immunopharmacol ; 130: 111691, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38367466

RESUMO

In the realm of fibroinflammatory conditions, chronic pancreatitis (CP) stands out as a particularly challenging ailment, lacking a dedicated, approved treatment. The potential of Pirfenidone (PFD), a drug originally used for treating idiopathic pulmonary fibrosis (IPF), in addressing CP's fibrotic aspects has sparked new interest. This investigation focused on the role of PFD in diminishing fibrosis and immune response in CP, using a mouse model induced by caerulein. The research extended to in vitro studies examining the influence of PFD on pancreatic stellate cells' (PSCs) behavior and the polarization of macrophages into M1 and M2 types. Advanced techniques like RNA sequencing and comprehensive data analyses were employed to decode the molecular interactions of PFD with PSCs. Supplementary experiments using techniques such as quantitative real-time PCR, western blotting, and immunofluorescence were also implemented. Results showed a notable reduction in pancreatic damage in PFD-treated mice, manifested through decreased acinar cell atrophy, lower collagen deposition, and a reduction in macrophage presence. Further investigation revealed PFD's capacity to hinder PSCs' migration, growth, and activation, alongside a reduction in the production and secretion of extracellular matrix proteins. This effect is primarily achieved by interfering with signaling pathways such as TGF-ß/Smad, Wnt/ß-catenin, and JAK/STAT. Additionally, PFD selectively hampers M1 macrophage polarization through the STAT3 pathway, without impacting M2 polarization. These outcomes highlight PFD's dual mechanism in moderating PSC activity and M1 macrophage polarization, positioning it as a promising candidate for CP therapy.


Assuntos
Células Estreladas do Pâncreas , Pancreatite Crônica , Piridonas , Humanos , Células Estreladas do Pâncreas/metabolismo , Células Estreladas do Pâncreas/patologia , Pancreatite Crônica/tratamento farmacológico , Pancreatite Crônica/induzido quimicamente , Pâncreas/patologia , Macrófagos/metabolismo , Fibrose
20.
Environ Sci Technol ; 58(10): 4476-4486, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38382547

RESUMO

Antibiotic resistance genes (ARGs) are ancient but have become a modern critical threat to health. Gut microbiota, a dynamic reservoir for ARGs, transfer resistance between individuals. Surveillance of the antibiotic resistome in the gut during different host growth phases is critical to understanding the dynamics of the resistome in this ecosystem. Herein, we disentangled the ARG profiles and the dynamic mechanism of ARGs in the egg and adult phases of Tetramorium caespitum. Experimental results showed a remarkable difference in both gut microbiota and gut resistome with the development of T. caespitum. Meta-based metagenomic results of gut microbiota indicated the generalizability of gut antibiotic resistome dynamics during host development. By using Raman spectroscopy and metabolomics, the metabolic phenotype and metabolites indicated that the biotic phase significantly changed lipid metabolism as T. caespitum aged. Lipid metabolites were demonstrated as the main factor driving the enrichment of ARGs in T. caespitum. Cuminaldehyde, the antibacterial lipid metabolite that displayed a remarkable increase in the adult phase, was demonstrated to strongly induce ARG abundance. Our findings show that the gut resistome is host developmental stage-dependent and likely modulated by metabolites, offering novel insights into possible steps to reduce ARG dissemination in the soil food chain.


Assuntos
Antibacterianos , Formigas , Genes Bacterianos , Humanos , Adulto , Idoso , Antibacterianos/farmacologia , Ecossistema , Lipídeos
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