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1.
BMC Med ; 22(1): 101, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448943

RESUMEN

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS: Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS: A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS: The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.


Asunto(s)
Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Factores de Riesgo , Bases de Datos Factuales , Pacientes
2.
Org Biomol Chem ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177493

RESUMEN

A general and efficient method has been developed to access axially chiral 2-arylpyrroles using catalytic asymmetric Suzuki-Miyaura cross-coupling. A wide range of axially chiral arylpyrroles were obtained in high yields with good to excellent enantioselectivities. The key to success is the use of a combined catalytic system involving a palladium catalyst and chiral ferrocene diphosphine ligand for achieving effective enantiocontrol. More importantly, this axially chiral CF3-substituted 2-arylpyrrole serves as a key intermediate in the preparation of the anti-hypertensive and diabetic nephropathy drug esaxerenone. It was directly asymmetrically synthesized with high enantioselectivity (92% ee). Thus, a new strategy is provided for the catalytic asymmetric synthesis of esaxerenone.

3.
Bioorg Chem ; 148: 107453, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38761708

RESUMEN

Thirty-five trifluoromethyl hydrazones and seventeen trifluoromethyl oxime esters were designed and synthesized via molecular hybridization. All the target compounds were initially screened for in vitro anti-inflammatory activity by assessing their inhibitory effect on NO release in LPS-stimulated RAW264.7 cells, and the optimal compound was finally identified as 2-(3-Methoxyphenyl)-N'-((6Z,9Z,12Z,15Z)-1,1,1-trifluorohenicosa-6,9,12,15-tetraen-2-ylidene)acetohydrazide (F26, IC50 = 4.55 ± 0.92 µM) with no cytotoxicity. Moreover, F26 potently reduced the production of PGE2 in LPS-stimulated RAW264.7 cells compared to indomethacin. The interaction of F26 with COX-2 and cPLA2 was directly verified by the CETSA technique. F26 was found to modulate the phosphorylation levels of p38 MAPK and NF-κB p65, as well as the protein expression of IκB, cPLA2, COX-2, and iNOS in LPS-stimulated rat peritoneal macrophages. Additionally, F26 was observed to prevent the nuclear translocation of NF-κB p65 in LPS-stimulated rat peritoneal macrophages by immunofluorescence localization. Therefore, the aforementioned in vitro experiments demonstrated that F26 blocked the p38 MAPK and NF-κB pathways by binding to COX-2 and cPLA2. In the adjuvant-induced arthritis model, F26 demonstrated a significant effect in preventing arthritis symptoms and inflammatory status in rats, exerting an immunomodulatory role by regulating the homeostasis between Th17 and Treg through inhibition of the p38 MAPK/cPLA2/COX-2/PGE2 and NF-κB pathways. Encouragingly, F26 caused less acute ulcerogenicity in rats at a dose of 50 mg/kg compared to indomethacin. Overall, F26 is a promising candidate worthy of further investigation for treating inflammation and associated pain with lesser gastrointestinal irritation, as well as other symptoms in which cPLA2 and COX-2 are implicated in the pathophysiology.


Asunto(s)
Artritis Reumatoide , Inhibidores de la Ciclooxigenasa 2 , Ciclooxigenasa 2 , Animales , Ratones , Ciclooxigenasa 2/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Células RAW 264.7 , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/química , Inhibidores de la Ciclooxigenasa 2/síntesis química , Ratas , Relación Estructura-Actividad , Estructura Molecular , Inflamación/tratamiento farmacológico , Masculino , Relación Dosis-Respuesta a Droga , Cetonas/química , Cetonas/farmacología , Cetonas/síntesis química , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/síntesis química , Fosfolipasas A2/metabolismo , Administración Oral , Ratas Sprague-Dawley
4.
Bioorg Chem ; 153: 107805, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39255608

RESUMEN

A series of 3-(2-trifluoromethyl-3-aryl-4H-chromen-4-yl)-1H-indoles (5-1 to 5-29) were developed and characterized. Most of compounds were found to be potent for inhibiting the production of NO in LPS-induced RAW264.7 cells, of which 3-(3-(4-chlorophenyl)-6-methoxy-2-(trifluoromethyl)-4H-chromen-4-yl)-1H-indole (5-25) was the most optimal (IC50 = 4.82 ± 0.34 µΜ) and was capable of significantly suppressing the release of PGE2. The inhibitory effect of 5-25 on human recombinant COX-2 (IC50 = 51.7 ± 1.3 nM) was measured and molecular docking was performed, determining 5-25 as a COX-2 inhibitor. Additionally, the interaction between 5-25 and COX-2 was determined by the CETSA technique. Then, 5-25 inhibited the degradation of IκB, the phosphorylation and nuclear translocation of NF-κB p65, and the expression of COX-2 and iNOS. Moreover, it was verified that 5-25 exhibited efficacy in rodent models of inflammation and pain, encompassing the paw edema, cotton pellet-induced granuloma, acid-induced writhing, and adjuvant-induced arthritis models. Therefore, the mechanism of 5-25 may be to bind to COX-2 and exert anti-inflammatory and analgesic effects in vitro and in vivo by suppressing the NF-κB pathway. Encouragingly, in comparison with indomethacin, 5-25 exhibited a lower ulcerative potential in rats, as manifested by generating smaller areas and fewer ulcers, less inflammatory infiltration, a lower expression of MMP-9, and less apoptosis. In conclusion, 5-25 is a candidate drug with high activity and low ulcerogenic potential, and it deserves further research for the treatment of inflammation, pain, and other symptoms in which COX-2 plays a role in their pathogenesis.

5.
Environ Res ; 250: 118539, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38401684

RESUMEN

The relationship of exposure to benzo[a]pyrene (BaP) with lung cancer risk has been firmly established, but whether this association could be modified by other environmental or genetic factors remains to be explored. To investigate whether and how zinc (Zn) and genetic predisposition modify the association between BaP and lung cancer, we performed a case-cohort study with a 5.4-year median follow-up duration, comprising a representative subcohort of 1399 participants and 359 incident lung cancer cases. The baseline concentrations of benzo[a]pyrene diol epoxide-albumin adduct (BPDE-Alb) and Zn were quantified. We also genotyped the participants and computed the polygenic risk score (PRS) for lung cancer. Our findings indicated that elevated BPDE-Alb and PRS were linked to increased lung cancer risk, with the HR (95%CI) of 1.54 (1.36, 1.74) per SD increment in ln-transformed BPDE-Alb and 1.27 (1.14, 1.41) per SD increment in PRS, but high plasma Zn level was linked to a lower lung cancer risk [HR (95%CI)=0.77 (0.66, 0.91) per SD increment in ln-transformed Zn]. There was evidence of effect modification by Zn on BaP-lung cancer association (P for multiplicative interaction = 0.008). As Zn concentrations increased from the lowest to the highest tertile, the lung cancer risk per SD increment in ln-transformed BPDE-Alb decreased from 2.07 (1.48, 2.89) to 1.33 (0.90, 1.95). Additionally, we observed a significant synergistic interaction of BPDE-Alb and PRS [RERI (95%CI) = 0.85 (0.03, 1.67)], with 42% of the incident lung cancer cases among individuals with high BPDE-Alb and high PRS attributable to their additive effect [AP (95%CI) = 0.42 (0.14, 0.69)]. This study provided the first prospective epidemiological evidence that Zn has protective effect against BaP-induced lung tumorigenesis, whereas high genetic risk can enhance the harmful effect of BaP. These findings may provide novel insight into the environment-environment and environment-gene interaction underlying lung cancer development, which may help to develop prevention and intervention strategies to manage BaP-induced lung cancer.


Asunto(s)
Benzo(a)pireno , Neoplasias Pulmonares , Zinc , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/epidemiología , Benzo(a)pireno/toxicidad , Zinc/sangre , Persona de Mediana Edad , Masculino , China/epidemiología , Femenino , Estudios Prospectivos , Anciano , Exposición a Riesgos Ambientales/efectos adversos , Predisposición Genética a la Enfermedad , Factores de Riesgo , Estudios de Casos y Controles , Adulto , Puntuación de Riesgo Genético , Pueblos del Este de Asia
6.
Environ Res ; 263(Pt 1): 120038, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39305974

RESUMEN

The rapidly rising risk of cognitive decline is a serious challenge for the elderly. As the wide-distributed environmental chemicals, the effects of metals exposure on cognitive function have attracted much attention, but the results remain inclusive. This study aimed to investigate the roles of multiple metals co-exposure on cognition. We included a total of 6112 middle-aged and older participants, detected their plasma levels of 23 metals by using inductively coupled plasma mass spectrometry, and assessed their cognitive function by using the Mini-Mental State Examination (MMSE). The results showed that increased plasma levels of iron (Fe) and zinc (Zn) were positively associated with MMSE score, but the increased levels of nickel (Ni) and lead (Pb) were associated with decreased MMSE score (all FDR < 0.05). Subjects exposed to both high levels of Ni and Pb showed the lowest MMSE score [ß (95% CI) = -0.310 (-0.519, -0.100)], suggesting that Ni and Pb had a synergistic toxic effect on cognitive function. In addition, the hazardous roles of Ni and Pb were mainly found among subjects with low plasma level of Zn, but were not significant among those with high-Zn level [Ni: ß (95% CI) = -0.281 (-0.546, -0.015) vs. -0.146 (-0.351, 0.058); Pb: ß (95% CI) = -0.410 (-0.651, -0.169) vs. -0.060 (-0.275, 0.155)], which suggested that Zn could attenuate the adverse effects of Pb and Ni on cognitive function. The cognitive function was gradually decreased among subjects with increased number of adverse exposures to the above four metals (Ptrend < 0.001). In conclusion, our findings revealed the individual, interactive, and combined effects of Fe, Ni, Pb, and Zn on cognitive function, which may provide new perspectives on cognitive protection, but further prospective cohort studies and biological researches are needed to validate these findings.

7.
BMC Pediatr ; 24(1): 562, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232719

RESUMEN

BACKGROUND: With the widespread use of antibiotics, more attention has been paid to their side effects. We paid extra attention to the impact of antibiotics on children's bodies. Therefore, we analyzed the characteristic changes in the gut microbiota of children after antibiotic treatment to explore the pathogenesis of antibiotic-associated diseases in more depth and to provide a basis for diagnosis and treatment. METHODS: We recruited 28 children with bronchopneumonia in the western district of Zhuhai, China, and divided them into three treatment groups based on antibiotic type. We took stool samples from children before and 3-5 days after antibiotic treatment. 16S rRNA gene sequencing was used to analyze the effects of antibiotic therapy on the gut microbiota of children. Continuous nonparametric data are represented as median values and analyzed using the Wilcoxon rank-sum test. RESULTS: While alpha diversity analysis found no significant changes in the mean abundance of the gut microbiota of children after a short course of antibiotic treatment, beta diversity analysis demonstrated significant changes in the composition and diversity of the gut microbiota of children even after a short course of antibiotic therapy. We also found that meloxicillin sulbactam can inhibit the growth of Proteobacteria, Bacteroidetes, and Verrucomicrobia, ceftriaxone inhibits Verrucomicrobia and Bacteroides, and azithromycin inhibits Fusobacteria, Actinobacteria, Proteobacteria, and Verrucomicrobia. We further performed a comparative analysis at the genus level and found significantly different clusters in each group. Finally, we found that azithromycin had the greatest effect on the metabolic function of intestinal microbiota, followed by ceftriaxone, and no significant change in the metabolic process of intestinal microbiota after meloxicillin sulbactam treatment. CONCLUSIONS: Antibiotic treatment significantly affects the diversity of intestinal microbiota in children, even after a short course of antibiotic treatment. Different classes of antibiotics affect diverse microbiota primarily, leading to varying alterations in metabolic function. Meanwhile, we identified a series of intestinal microbiota that differed significantly after antibiotic treatment. These groups of microbiota could be used as biomarkers to provide an additional basis for diagnosing and treating antibiotic-associated diseases.


Asunto(s)
Antibacterianos , Microbioma Gastrointestinal , ARN Ribosómico 16S , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Masculino , Femenino , Estudios de Casos y Controles , Lactante , Preescolar , Heces/microbiología , Niño , Análisis de Secuencia de ARN
8.
Ecotoxicol Environ Saf ; 271: 115980, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38262095

RESUMEN

Epidemiologic studies have reported the positive relationship of benzo[a]pyrene (BaP) exposure with the risk of lung cancer. However, the mechanisms underlying the relationship is still unclear. Plasma microRNA (miRNA) is a typical epigenetic biomarker that was linked to environment exposure and lung cancer development. We aimed to reveal the mediation effect of plasma miRNAs on BaP-related lung cancer. We designed a lung cancer case-control study including 136 lung cancer patients and 136 controls, and measured the adducts of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) and sequenced miRNA profiles in plasma. The relationships between BPDE-Alb adducts, normalized miRNA levels and the risk of lung cancer were assessed by linear regression models. The mediation effects of miRNAs on BaP-related lung cancer were investigated. A total of 190 plasma miRNAs were significantly related to lung cancer status at Bonferroni adjusted P < 0.05, among which 57 miRNAs showed different levels with |fold change| > 2 between plasma samples before and after tumor resection surgery at Bonferroni adjusted P < 0.05. Especially, among the 57 lung cancer-associated miRNAs, BPDE-Alb adducts were significantly related to miR-17-3p, miR-20a-3p, miR-135a-5p, miR-374a-5p, miR-374b-5p, miR-423-5p and miR-664a-5p, which could in turn mediate a separate 42.2%, 33.0%, 57.5%, 36.4%, 48.8%, 32.5% and 38.2% of the relationship of BPDE-Alb adducts with the risk of lung cancer. Our results provide non-invasion biomarker candidates for lung cancer, and highlight miRNAs dysregulation as a potential intermediate mechanism by which BaP exposure lead to lung tumorigenesis.


Asunto(s)
Neoplasias Pulmonares , MicroARNs , Humanos , MicroARNs/genética , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/genética , Benzo(a)pireno/toxicidad , 7,8-Dihidro-7,8-dihidroxibenzo(a)pireno 9,10-óxido/toxicidad , Estudios de Casos y Controles , Pulmón , Biomarcadores , China
9.
BMC Microbiol ; 23(1): 237, 2023 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-37641037

RESUMEN

BACKGROUND: Despite the growing interest in the impact of the gut microbiome on cancer, the relationship between the lung microbiome and lung cancer has received limited investigation. Additionally, the composition of the oral microbiome was found to differ from that of individuals with lung cancer, indicating that these microorganisms may serve as potential biomarkers for the detection of lung cancer. METHODS: Forty-three Chinese lung cancer patients were enrolled in the current retrospective study and 16 S rRNA sequencing was performed on saliva, cancerous tissue (CT) and paracancerous tissue (PT) samples. RESULTS: Diversity and species richness were significantly different between the oral and lung microbiota. Lung microbiota were largely composed of the phyla Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria. The relative abundance of Promicromonosporacea and Chloroflexi increased in CT, while Enterococcaceae and Enterococcus were enriched in PT (p<0.05). A cancer-related microbiota model was constructed and produced an area under the curve of 0.74 in the training set, indicating discrimination between subjects with and without cancer. CONCLUSIONS: Characterization of microbiota in saliva, CT and PT from Chinese lung cancer patients revealed little difference between CT and PT, indicating that the tumor and its microenvironment might influence the local microbiome. A model to distinguish between CT and PT was constructed, which has the potential to enhance our comprehension of the involvement of microbiota in the pathogenesis of lung cancer and identify novel therapeutic targets.


Asunto(s)
Neoplasias Pulmonares , Microbiota , Humanos , Saliva , Pueblos del Este de Asia , Estudios Retrospectivos , Microbiota/genética , Microambiente Tumoral
10.
Cytokine ; 170: 156294, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37549487

RESUMEN

BACKGROUND: Premature ovarian failure (POF), as a gynecological endocrine disease, features the manifestation of irregular menstruation, amenorrhea, infertility and perimenopausal syndrome. MicroRNAs (miRNAs) have been reported to modulate POF. However, the specific regulatory mechanism of miR-497-3p in POF remain unclear. METHODS: Quantitative reverse transcription-PCR (RT-qPCR) and western blot were implemented to analyze RNA and protein levels, respectively. Comet assay was performed for the detection of DNA damage. Flow cytometry analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed to measure apoptosis of CTX-induced KGN cell (POF cell model). Bioinformatics was utilized to screen out the downstream mRNAs potentially regulated by miR-497-3p. Chromatin immunoprecipitation (ChIP) assay, luciferase reporter assay and RNA pulldown assays were performed to demonstrate the interaction between miR-497-3p and Kruppel-like factor 4 (KLF4) or between KLF4 and Klotho (KL). Rescue assays were performed to verify the involvement of Klotho in miR-497-3p-mediated functions of POF cell model. RESULTS: MiR-497-3p was upregulated in CTX-treated KGN cells. Knockdown of miR-497-3p could reverse the promoting effects of CTX on DNA damage and cell apoptosis. MiR-497-3p negatively regulated Klotho expression by directly targeting the transcription activator KLF4. KLF4 activated Klotho transcription. MiR-497-3p inactivated PI3K/AKT/mTOR signaling pathway through KLF4/Klotho axis. Klotho knockdown reversed the effects of MiR-497-3p on the functions of POF cell model. CONCLUSION: MiR-497-3p promotes DNA damage and apoptosis in CTX-treated KGN cells by targeting KLF4 to downregulate Klotho and inactivate the PI3K/AKT/mTOR signaling pathway. This study unveils novel mechanisms associated with cell functional changes in POF and may enrich therapeutic strategy for POF.


Asunto(s)
Menopausia Prematura , MicroARNs , Insuficiencia Ovárica Primaria , Femenino , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Insuficiencia Ovárica Primaria/genética , Factor 4 Similar a Kruppel , Transducción de Señal/genética , MicroARNs/genética , MicroARNs/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Apoptosis/genética , Proliferación Celular/genética , Línea Celular Tumoral
11.
Environ Res ; 237(Pt 1): 116911, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37597825

RESUMEN

Nitrate (NO3-) pollution of groundwater is a global concern in agricultural areas. To gain a comprehensive understanding of the sources and destiny of nitrate in soil and groundwater within intensive agricultural areas, this study employed a combination of chemical indicators, dual isotopes of nitrate (δ15N-NO3- and δ18O-NO3-), random forest model, and Bayesian stable isotope mixing model (MixSIAR). These approaches were utilized to examine the spatial distribution of NO3- in soil profiles and groundwater, identify key variables influencing groundwater nitrate concentration, and quantify the sources contribution at various depths of the vadose zone and groundwater with different nitrate concentrations. The results showed that the nitrate accumulation in the cropland and kiwifruit orchard at depths of 0-400 cm increased, leading to subsequent leaching of nitrate into deeper vadose zones and ultimately groundwater. The mean concentration of nitrate in groundwater was 91.89 mg/L, and 52.94% of the samples exceeded the recommended grade III value (88.57 mg/L) according to national standards. The results of the random forest model suggested that the main variables affecting the nitrate concentration in groundwater were well depth (16.6%), dissolved oxygen (11.6%), and soil nitrate (10.4%). The MixSIAR results revealed that nitrate sources vary at different soil depths, which was caused by the biogeochemical process of nitrate. In addition, the highest contribution of nitrate in groundwater, both with high and low concentrations, was found to be soil nitrogen (SN), accounting for 56.0% and 63.0%, respectively, followed by chemical fertilizer (CF) and manure and sewage (M&S). Through the identification of NO3- pollution sources, this study can take targeted measures to ensure the safety of groundwater in intensive agricultural areas.

12.
Environ Res ; 216(Pt 1): 114509, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36208786

RESUMEN

OBJECTIVE: Mitochondria are essential organelles that execute fundamental biological processes, while mitochondrial DNA is vulnerable to environmental insults. The aim of this study was to investigate the individual and mixture effect of plasma metals on blood mitochondria DNA copy number (mtDNAcn). METHODS: This study involved 1399 randomly selected subcohort participants from the Dongfeng-Tongji cohort. The blood mtDNAcn and plasma levels of 23 metals were determined by using quantitative real-time polymerase chain reaction (qPCR) and inductively coupled plasma mass spectrometer (ICP-MS), respectively. The multiple linear regression was used to explore the association between each metal and mtDNAcn, and the LASSO penalized regression was performed to select the most significant metals. We also used the quantile g-computation analysis to assess the mixture effect of multiple metals. RESULTS: Based on multiple linear regression models, each 1% increase in plasma concentration of copper (Cu), rubidium (Rb), and titanium (Ti) was associated with a separate 0.16% [ß(95% CI) = 0.158 (0.066, 0.249), P = 0.001], 0.20% [ß(95% CI) = 0.196 (0.073, 0.318), P = 0.002], and 0.25% [ß(95% CI) = 0.245 (0.081, 0.409), P = 0.003] increase in blood mtDNAcn. The LASSO regression also confirmed Cu, Rb, and Ti as significant predictors for mtDNAcn. There was a significant mixture effect of multiple metals on increasing mtDNAcn among the elder participants (aged ≥65), with an approximately 11% increase in mtDNAcn for each quartile increase in all metal concentrations [ß(95% CI) = 0.146 (0.048, 0.243), P = 0.004]. CONCLUSIONS: Our results show that plasma Cu, Rb and Ti were associated with increased blood mtDNA, and we further revealed a significant mixture effect of all metals on mtDNAcn among elder population. These findings may provide a novel perspective on the effect of metals on mitochondrial dysfunction.


Asunto(s)
Variaciones en el Número de Copia de ADN , ADN Mitocondrial , Humanos , Anciano , Estudios Transversales , Mitocondrias/genética , Estudios de Cohortes , Metales
13.
Int J Med Sci ; 20(9): 1220-1234, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37575275

RESUMEN

Purpose: Melanoma is a highly malignant tumor, which metastasizes and has poor prognosis in late-stage cancer patients. α-Mangostin possesses pharmacological properties, including antioxidant, anti-infective, and anticarcinogenic activities. We investigated α-Mangostin effect on melanoma growth, migration, and invasion and its possible molecular mechanism. Methods: Melanoma cells growth inhibition was determined by the colorimetric 4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. Morphological changes of α-Mangostin-treated melanoma cells were evaluated by transmission electron microscopy and JC-1 staining. Cell apoptosis and cell cycle arrest were assessed by flow cytometry. The effect of α-Mangostin on tumor cells migration and invasion was observed by migration and invasion in vitro assay. Furthermore, the nude and C57BL/6 mouse subcutaneous melanoma models were used to evaluate the in vivo anti-tumor effect of α-Mangostin. Western blot and real time-PCR were performed to analyze the influence of α-Mangostin on some of the common signaling pathways in melanoma cell lines. Signaling pathways were further verified in dissected tumor tissues. Results: α-Mangostin inhibited in vitro melanoma cells proliferation, migration, and invasion of melanoma cells, induced cell cycle arrest in G0/G1 phase, and caused mitochondrial swelling and membrane depolarization, whereas it effectively suppressed melanoma growth in xenografted mice. In addition, α-Mangostin potentiated the in vitro and in vivo anti-tumor effects of cisplatin both in vitro and in vivo. Mechanistically, α-Mangostin down-regulated expression of RAS protein and mRNA, as well as phosphorylation of PI3K in A375, B16F10, M14 and SK-MEL-2 cells. MITF protein and mRNA were inhibited only in M14 cells. Conclusion: α-Mangostin suppresses melanoma cells growth, migration and invasion, and synergistically enhances the anti-tumor effect of chemotherapy, whose mechanism may be mediated through inhibiting Ras, PI3K and MITF.


Asunto(s)
Melanoma , Animales , Ratones , Línea Celular Tumoral , Ratones Endogámicos C57BL , Melanoma/tratamiento farmacológico , Proliferación Celular , Apoptosis , ARN Mensajero , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Movimiento Celular
14.
J Environ Manage ; 325(Pt A): 116449, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36252329

RESUMEN

Climate change alters weather patterns and hydrological cycle, thus potentially aggravating water quality impairment. However, the direct relationships between climate variability and water quality are complicated by a multitude of hydrological and biochemical mechanisms dominate the process. Thus, little is known regarding how water quality responds to climate variability in the context of changing meteorological conditions and human activities. Here, a longitudinal study was conducted using trend, correlation, and redundancy analyses to explore stream water quality sensitivity to temperature, precipitation, streamflow, and how the sensitivity was affected by watershed climate, land cover percentage, landscape configuration, fertilizer application, and tillage types. Specifically, daily pollutant concentration data of suspended solid (SS), total phosphorus (TP), soluble reactive phosphorus (SRP), total Kjeldahl nitrogen (TKN), nitrate and nitrite (NOx), and chloride (Cl) were used as water quality indicators in four Lake Erie watersheds from 1985 to 2017, during which the average temperature has increased 0.5 °C and the total precipitation has increased 9%. Results show that precipitation and flow were positively associated with SRP, NOx, TKN, TP, and SS, except for SRP and NOx in the urban basin. The rising temperatures led to increasing concentrations of SS, TKN, and TP in the urban basin. SRP and NOx sensitivity to precipitation was higher in the years with more precipitation and higher precipitation seasonality, and the basins with more spatially aggregated cropland. No-tillage and reduced tillage management could decrease both precipitation and temperature sensitivity for most pollutants. As one of the first studies leveraging multiple watershed environmental variables with long-term historical climate and water quality data, this study can assist target land use planning and management policy to mitigate future climate change effects on surface water quality.


Asunto(s)
Lagos , Calidad del Agua , Humanos , Estudios Longitudinales , Monitoreo del Ambiente , Fósforo/análisis , Ríos , Nitrógeno/análisis , Cambio Climático
15.
Energy Build ; 286: 112975, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-38213397

RESUMEN

Investigation of housing indoor temperature is important for understanding the comfort, health and living conditions of the local residents. The traditional method to measure indoor temperature is to place sensors at the target places, which is not only expensive but also inconvenient for indoor temperature investigation, especially for the investigation at community and city scale. In this study, a novel method was proposed to obtain the indoor temperatures remotely from outside the building through window opening area using and infrared camera. Compared with the traditional contact measurement method, the proposed remote sensing method could detect the indoor temperature without entering the room. Moreover, the infrared image could reflect the spatial distribution information of indoor temperature. To verify the feasibility and accuracy of this method, an experiment was conducted in a test room under heating, transitional, and cooling conditions with various window opening grades. It was found that the infrared images at the window opening area could reflect the spatial distribution of indoor temperature with an accuracy within 0.5 °C under stable heating and transitional conditions. In the fan coil cooling condition, however, although the infrared image can reflect the cold air flow pattern, the deviations between the infrared temperature and the measured room temperature exceeded 1.0 °C. The effect of window opening grade on the recognition accuracy kept within 0.5 °C.

16.
Ecotoxicol Environ Saf ; 230: 113156, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34979313

RESUMEN

The effect of water source on cognitive functioning is poorly understood. The present study explored the associations between water source and cognition in 9921 participants from the China Health and Retirement Longitudinal Study (CHARLS). Cognitive functioning was measured from three aspects: orientation and attention, episodic memory, and visuo-construction. Water sources included tap and non-tap water. Generalized linear models and multiple logistic regression models were conducted to investigate the associations of cognitive scores with water source among the whole population and different subgroups. Results from cross-sectional analysis reported that participants without access to tap water showed a lower cognitive score (ß = - 0.57; 95% CI: - 0.74, - 0.39) than those with tap water as a water source; and this phenomenon was pronounced for both sexes and across all residences. During 4-years' follow-up, a greater decline of cognitive score was associated with no tap water use in the lowest quartile of baseline cognitive scores (ß = - 0.67; 95% CI: - 1.26, - 0.08). Additionally, the utilization rate of tap water was lower in rural areas compared to urban areas. The lowest utilization rates were observed in urban areas of the Anhui province (0.38 in 2011 and 0.55 in 2015) and in rural areas of Inner Mongolia (0.09 in 2011 and 0.20 in 2015). These findings suggest that having no tap water may be a risk factor for cognition impairment, particularly for those with a low basic cognition score. Additionally, our results support the need to expand tap water use in China.

17.
Ecotoxicol Environ Saf ; 248: 114284, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36395653

RESUMEN

BACKGROUND: Associations of air pollution with anxiety and depression were found in previous studies. However, whether air pollution exposure during pregnancy contributes to prenatal anxiety and depression or not is under-investigated. In this study, we aimed to analyze associations between fine particulate matter (PM2.5) exposure with anxiety and depression during pregnancy and to explore the critical window of PM2.5 exposure. METHODS: This study was based on the Shanghai Maternal-Child Pairs Cohort (Shanghai MCPC). We used a gap-filling random forest model to estimate PM2.5 exposure concentration during pregnancy of each participant. The Self-Rating Anxiety Scale (SAS) and the Center for Epidemiological Survey-Depression Scale (CES-D) were used to quantify the anxiety and depression levels in late pregnancy. Covariate information was obtained from medical records and questionnaires. We performed generalized linear regression and logistic regression models to assess the association and the critical window. RESULTS: Totally 3731 pregnant women were included, with the age of 28.85 ± 3.97 years old. Anxiety and depression rates were 10.8 % and 11.5 % respectively, according to the cut-off value of SAS and CES-D. Generalized linear regression results showed that the increase of PM2.5 concentration in three stages (gestational 0-13 weeks, 0-26 weeks, 0-36 weeks) was related to the increase of scale score. The PM2.5 concentration in 0-13 weeks could increase the risk of anxiety and depression by approximately 23 % and 25 %, respectively. And the gestational weeks 4th-13th were the suspicious critical window of PM2.5 exposure. CONCLUSION: The increased risk of anxiety or depression was related to PM2.5 exposure during pregnancy, especially early pregnancy.


Asunto(s)
Depresión , Mujeres Embarazadas , Humanos , Femenino , Embarazo , Adulto Joven , Adulto , Depresión/epidemiología , China/epidemiología , Ansiedad/epidemiología , Vitaminas , Material Particulado/efectos adversos
18.
Inorg Chem ; 60(12): 8870-8879, 2021 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-34097386

RESUMEN

Silicate phosphor KBaScSi2O7:Ce3+ (KBSS:Ce3+), as a novel material, has been prepared by the solid-state method in this study. The crystal structure, luminescent properties, thermal stability, and cathodoluminescence (CL) properties of this material were analyzed systematically. It concludes that the phosphor can emit cyan light with emission peak at 509 nm under n-UV light excitation (300-400 nm). By coating KBSS:Ce3+ with a red-emitting CaAlSiN3:Eu2+ on a n-UV (365 nm) light-emitting diode (LED) chip, the intense warm white light with high RA (83.4) and low CCT (3652) can be produced under a 350 mA forward bias current.In addition, the CL performance shows that KBSS:0.10Ce3+ has high saturation current and voltage and good color stability under low voltage conditions. All these results indicate that KBSS:Ce3+ phosphor will be very promising in LED and field emission display applications.

19.
BMC Pediatr ; 21(1): 277, 2021 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-34126969

RESUMEN

BACKGROUND: Kawasaki disease (KD) is the main cause of acquired heart disease in children and can lead to coronary artery lesions. This present study was designed to analyze the characteristics of KD peripheral blood mononuclear cells (PBMC) through single-cell RNA sequencing (scRNA-seq) and to explore the potential molecular mechanism of KD. METHODS: PBMC was collected from one healthy child and one KD patient, and was used to single-cell RNA sequencing for cell clusters identification and differently expressed gene (DEG) determination. GO function enrichment analysis of DEG in B cell and T cells were performed to explore the most active biological function in KD immune cells. RESULTS: Twelve cell clusters can be identified in two samples. Compared with healthy child, naive CD8+ T cell, T helper cell and B cell in KD child were decreased, mainly immune-related T cells, and natural killer T (NKT) cell were increased. Cell activation, lymphocyte activation and regulation of immune system process were 3 GO function shared by all four types of T cells and B cell. CONCLUSIONS: Immune cell disorder appears in the KD patient at single cell level by scRNA-seq.


Asunto(s)
Síndrome Mucocutáneo Linfonodular , Linfocitos T CD8-positivos , Niño , Vasos Coronarios , Humanos , Leucocitos Mononucleares , Síndrome Mucocutáneo Linfonodular/genética , Análisis de Secuencia de ARN
20.
Ecotoxicol Environ Saf ; 224: 112645, 2021 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-34416639

RESUMEN

Gestational diabetes mellitus (GDM) has become a new global epidemic with a rapidly increasing prevalence. Previous studies have suggested that air pollution is associated with GDM risk, but the results are inconsistent, and mechanistic studies are limited. Based on a hospital-based cohort, a total of 6374 participants were included in this study. Individual daily PM2.5 exposure at a 1-km resolution was predicted using a full-spatiotemporal-coverage model. The results of multiple linear regression showed that glycated hemoglobin (HbA1c) was significantly associated with PM2.5 both in the 1-month preconception and in the first trimester of pregnancy. Additionally, HbA1c decreased 0.437% (95% CI: -0.629, -0.244) as the serum 25-hydroxyvitamin D (25(OH)D) increased by one interquartile range (IQR) (9.2 ng/ml). An IQR increase in PM2.5 exposure was also negatively associated with serum 25(OH)D (estimated change% and 95% CI: -7.249 (-9.054, -5.408) in the 1-month preconception and - 13.069 (-15.111, -10.979) in the first trimester of pregnancy). Mediation analysis showed that serum 25(OH)D status mediated the association between HbA1c and PM2.5 exposure both in the preconception and in the first trimester (mediated percent: 2.00% and 4.05% (Sobel p<0.001), respectively). The result suggested a vicious cycle among PM2.5 exposure, lower serum VD status and a higher HbA1c. More studies are warranted since the protective effect of 25(OH)D against glucose disorders associated with air pollution in this study was limited.

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