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1.
Int Immunopharmacol ; 133: 112067, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608444

RESUMO

Silicosis is one of the most common and severe types of pneumoconiosis and is characterized by lung dysfunction, persistent lung inflammation, pulmonary nodule formation, and irreversible pulmonary fibrosis. The transdifferentiation of fibroblasts into myofibroblasts is one of the main reasons for the exacerbation of silicosis. However, the underlying mechanism of transcription factors regulating silicosis fibrosis has not been clarified. The aim of this study was to investigate the potential mechanism of transcription factor FOXF1 in fibroblast transdifferentiation in silica-induced pulmonary fibrosis. Therefore, a silicosis mouse model was established, and we found that FOXF1 expression level was significantly down-regulated in the silicosis group, and after overexpression of FOXF1 by adeno-associated virus (AAV), FOXF1 expression level was up-regulated, and silicosis fibrosis was alleviated. In order to further explore the specific regulatory mechanism of FOXF1 in silicosis, we established a fibroblasts transdifferentiation model induced by TGF-ß in vitro. In the model, the expression levels of SMAD2/3 and P-SMAD2/3 were up-regulated, but the expression levels of SMAD2/3 and P-SMAD2/3 were down-regulated, inhibiting transdifferentiation and accumulation of extracellular matrix after the overexpressed FOXF1 plasmid was constructed. However, after silencing FOXF1, the expression levels of SMAD2/3 and P-SMAD2/3 were further up-regulated, aggravating transdifferentiation and accumulation of extracellular matrix. These results indicate that the activation of FOXF1 in fibroblasts can slow down the progression of silicosis fibrosis by inhibiting TGF-ß/SMAD2/3 classical pathway, which provides a new idea for further exploration of silicosis treatment.

2.
Circ Res ; 134(5): 505-525, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38422177

RESUMO

BACKGROUND: Chronic overconsumption of lipids followed by their excessive accumulation in the heart leads to cardiomyopathy. The cause of lipid-induced cardiomyopathy involves a pivotal role for the proton-pump vacuolar-type H+-ATPase (v-ATPase), which acidifies endosomes, and for lipid-transporter CD36, which is stored in acidified endosomes. During lipid overexposure, an increased influx of lipids into cardiomyocytes is sensed by v-ATPase, which then disassembles, causing endosomal de-acidification and expulsion of stored CD36 from the endosomes toward the sarcolemma. Once at the sarcolemma, CD36 not only increases lipid uptake but also interacts with inflammatory receptor TLR4 (Toll-like receptor 4), together resulting in lipid-induced insulin resistance, inflammation, fibrosis, and cardiac dysfunction. Strategies inducing v-ATPase reassembly, that is, to achieve CD36 reinternalization, may correct these maladaptive alterations. For this, we used NAD+ (nicotinamide adenine dinucleotide)-precursor nicotinamide mononucleotide (NMN), inducing v-ATPase reassembly by stimulating glycolytic enzymes to bind to v-ATPase. METHODS: Rats/mice on cardiomyopathy-inducing high-fat diets were supplemented with NMN and for comparison with a cocktail of lysine/leucine/arginine (mTORC1 [mechanistic target of rapamycin complex 1]-mediated v-ATPase reassembly). We used the following methods: RNA sequencing, mRNA/protein expression analysis, immunofluorescence microscopy, (co)immunoprecipitation/proximity ligation assay (v-ATPase assembly), myocellular uptake of [3H]chloroquine (endosomal pH), and [14C]palmitate, targeted lipidomics, and echocardiography. To confirm the involvement of v-ATPase in the beneficial effects of both supplementations, mTORC1/v-ATPase inhibitors (rapamycin/bafilomycin A1) were administered. Additionally, 2 heart-specific v-ATPase-knockout mouse models (subunits V1G1/V0d2) were subjected to these measurements. Mechanisms were confirmed in pharmacologically/genetically manipulated cardiomyocyte models of lipid overload. RESULTS: NMN successfully preserved endosomal acidification during myocardial lipid overload by maintaining v-ATPase activity and subsequently prevented CD36-mediated lipid accumulation, CD36-TLR4 interaction toward inflammation, fibrosis, cardiac dysfunction, and whole-body insulin resistance. Lipidomics revealed C18:1-enriched diacylglycerols as lipid class prominently increased by high-fat diet and subsequently reversed/preserved by lysine/leucine/arginine/NMN treatment. Studies with mTORC1/v-ATPase inhibitors and heart-specific v-ATPase-knockout mice further confirmed the pivotal roles of v-ATPase in these beneficial actions. CONCLUSION: NMN preserves heart function during lipid overload by preventing v-ATPase disassembly.


Assuntos
Cardiomiopatias , Resistência à Insulina , Animais , Camundongos , Ratos , Adenosina Trifosfatases , Arginina , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/prevenção & controle , Antígenos CD36/genética , Fibrose , Inflamação , Leucina , Lipídeos , Lisina , Alvo Mecanístico do Complexo 1 de Rapamicina , Miócitos Cardíacos , Mononucleotídeo de Nicotinamida , Receptor 4 Toll-Like/genética
3.
J Ethnopharmacol ; 326: 117926, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38369064

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana species, known as the traditional Tibetan medicine "Bangjian," have been integral to clinical practice for millennia. Despite their longstanding use, our understanding of the variation in chemical constituents and bioactive effects among different species is limited. AIM OF THE STUDY: In the present study, we aimed to assess the differences in chemical profiles and bioactivities among four Gentiana species (G. veitchiorum, G. trichotoma, G. crassuloides, and G. squarrosa) and explore potential bioactive markers. MATERIALS AND METHODS: The chemical composition of the four Gentiana species was analyzed using UPLC-QE-Orbitrap-MS. The antioxidant activity of the extracts was compared through DPPH, ABTS, and reducing power assays. The anti-inflammatory activity was evaluated by measuring the inhibitory effects on lipopolysaccharide-induced secretion of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) by RAW264.7 macrophages. Additionally, compounds strongly correlated with anti-inflammatory and antioxidant activities were identified through spectrum-effect relationship analysis. RESULTS: A total of 50 compounds were identified across the four Gentiana species. In vitro antioxidant assays demonstrated DPPH and ABTS scavenging abilities and reducing power within the concentration range of 62.5-2000 µg/mL. All four species inhibited the production of NO, IL-6, and TNF-α in RAW264.7 cells. Spectrum-effect relationship analysis revealed that gentiascabraside A, gentiatibetine, tachioside, lutonarin, and isotachioside were associated with the highest antioxidant activity; and swertiamarin, tarennoside, eleganoside C, and alpigenoside were associated with the highest anti-inflammatory activity. CONCLUSIONS: This study presents, for the first time, the chemical profiles and bioactivities of G. trichotoma, G. crassuloides, and G. squarrosa, which were comprehensively compared with those of G. veitchiorum. The findings provide novel insights to understand the traditional use and/or expand the current use of Gentiana species. Additionally, this research highlights the potential of Gentiana species as natural sources of antioxidants and anti-inflammatory agents, suggesting promising applications in tea production or medicinal contexts in the near future.


Assuntos
Benzotiazóis , Gentiana , Ácidos Sulfônicos , Gentiana/química , Antioxidantes/farmacologia , Antioxidantes/química , Extratos Vegetais/química , Tibet , Fator de Necrose Tumoral alfa , Interleucina-6 , Anti-Inflamatórios/farmacologia
5.
Front Immunol ; 14: 1249731, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928544

RESUMO

Introduction: OAS1(2'-5'-oligoadenylate synthetase 1) is a member of the Interferon-Stimulated Genes which plays an important role in the antiviral process. In recent years, the role of OAS1 in tumors has attracted attention, and it was found to be associated with prognosis in several tumors. However, the mechanism by which OAS1 affects tumors is unclear and pan-cancer study of OAS1 is necessary to better understand its implication in cancers. Methods: The expression, prognostic value, genetic alteration, alternative splicing events of OAS1 in pan-cancers were analyzed using TCGA, GTEx, HPA, GEPIA and OncoSplicing databases. OAS1 associated immune cell infiltration was evaluated using the ESTIMATE, xCell, CIBERSORT and QUANTISEQ algorithm. Single cell transcriptome data download using TISH database. Finally, the roles of the OAS1 on apoptosis, migration and invasion were investigated in two pancreatic cancer cells. Results: Our results revealed significant differences in OAS1 expression among various tumors, which had prognostic implications. In addition, we investigated the impact of OAS1 on genomic stability, methylation status, and other factors across different types of cancer, and the effects of these factors on prognosis. Notably, our study also demonstrated that OAS1 overexpression can contribute to CTL dysfunction and macrophage M2 polarization. In addition, cell experiments showed that the knockdown of OAS1 could reduce the invasive ability and increased the apoptosis rate of PAAD cells. Discussion: These results confirmed that OAS1 could be a prognostic biomarker and therapeutic target for its potential role in CTL dysfunction and macrophage M2 polarization.


Assuntos
Interferons , Neoplasias Pancreáticas , Humanos , Prognóstico , Multiômica , Biomarcadores , 2',5'-Oligoadenilato Sintetase/genética
6.
Chemosphere ; 345: 140497, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37866500

RESUMO

In this study, 26 typical antibiotics in the suspended matter of the Fen River basin were analyzed during the wet and dry seasons, and the main sources of antibiotic contamination were further identified. The results showed that the concentrations of antibiotics in the suspended matter varied seasonally. Sixteen antibiotics were detected in the suspended matter during the wet season with an average concentration of 463.56 ng/L. However, a total of 21 antibiotics were detected in the dry season, with an average concentration of 106.00 ng/L. The concentration of chloramphenicol antibiotics was outstanding in the wet season and dry season. The spatial distribution of the antibiotics in suspended matter showed little spatial discrepancy during the wet season. During the dry season, nevertheless, the concentration was higher upstream than midstream and downstream. The main sources of antibiotics in the Fen River Basin were livestock and poultry breeding, wastewater from wastewater treatment plants (WWTPs), agricultural drainage, domestic sewage, and pharmaceutical wastewater. Wastewater from WWTPs and domestic sewage were identified as two primary sources in the suspended matter during the wet season, with wastewater from WWTPs contributing the most accounting for 37%. While the most significant source of antibiotics in the suspended matter in the dry season was pharmaceutical wastewater, accounting for 36%. In addition, the contribution proportion of sources for antibiotics exhibited discrepant spatial distribution characteristics. In the wet season, wastewater from WWTPs dominated in the upstream and midstream, and livestock and poultry breeding was prominent in the midstream and downstream. Pharmaceutical wastewater was the main source in the midstream and downstream regions during the dry season.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Esgotos/análise , Antibacterianos/análise , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Estações do Ano , Preparações Farmacêuticas , China
7.
Biochem Biophys Res Commun ; 684: 149125, 2023 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-37897912

RESUMO

Ferroptosis, an emerging form of programmed cell death, has garnered substantial attention as a potential target for cancer therapy. However, despite the potential promise, no ferroptosis-related therapies have progressed to clinical trials. Identifying disease types sensitive to ferroptosis and developing specific ferroptosis-targeting drugs are critical focal points in the field of ferroptosis-based treatment. In this study, we conducted a comprehensive database analysis and presented compelling evidence indicating a high expression of GPX4 in patients with acute lymphoblastic leukemia (ALL), significantly correlating with poor prognosis. Notably, elevated GPX4 expression is closely associated with ALL relapse, a major challenge in the treatment of this disease. Building upon these findings, we devised a novel peptide-based Proteolysis Targeting Chimeras (PROTAC) drug targeting GPX4 through computer-aided design. In contrast to existing drugs that target the conjugative enzyme active site, our design focused on a peptide drug targeting the non-active site of GPX4. Furthermore, we strategically selected MDM2, an E3 ligase highly expressed in ALL, for the PROTAC drug design. This deliberate choice amplifies the drug's effect on cancer cells while minimizing its impact on normal cells, achieving desirable selectivity for cancer cells. Leveraging nanogold delivery, we successfully facilitated intracellular action of the GPX4-targeting peptide PROTAC drug, denoted as Au-PGPD (peptide GPX4 PROTAC drug). Au-PGPD effectively induced GPX4 degradation and inhibited ALL cell proliferation. Remarkably, Au-PGPD exhibited significantly less efficacy on normal cells, underscoring the selectivity and safety of our design.


Assuntos
Ferroptose , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Proteólise , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Peptídeos , Apoptose , Quimera de Direcionamento de Proteólise , Proteínas Proto-Oncogênicas c-mdm2
8.
Sensors (Basel) ; 23(17)2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37687879

RESUMO

A fuzzy PI controller was utilized to realize the modal matching between a driving and detecting model. A simulation model was built to study electrostatic decoupling controlling technology. The simulation results show that the modal matching can be gained by the fuzzy PI controller. The frequency difference between the driving mode and the detection mode is less than 1 Hz, and the offset of the input DC is smaller than 0.6 V. The optimal proportionality factor and integral coefficient are 1.5 and 20, respectively. The fuzzy PI controlling technology provides a good way for the parameter optimization to gain modal matching of micro gyro, via which the detecting accuracy and stability can be improved greatly.

9.
Toxics ; 11(7)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37505535

RESUMO

Chloramphenicol antibiotics (CAs) are broad-spectrum antibiotics which are widely used in the prevention and treatment of infectious diseases in livestock and poultry breeding. However, overused CAs can enter the watershed and eventually enter the sediment. Antibiotics in sediment can cause secondary pollution through disturbance and suspension. In this study, taking the Fenhe River Basin as the research area, the risk of CAs in sediment were assessed by collecting sediment samples. The results showed that CAs were detected in all sediment samples of the Fenhe River Basin. The mean concentration of CAs was 79.1 µg/kg, and the concentration of thiamphenicol (THI) was dominant, which was up to 58.3 µg/kg. Temporally, there are great differences in different seasons; the concentration of CAs was higher in winter than that in summer, up to 4.79-174 times. Spatially, the mean concentration of CAs in midstream was 83.5 µg/kg, which was higher than that in the upstream and downstream. The concentration of CAs in tributaries were generally higher than that in the main stream, and the mean concentration of tributaries was 1.1 times that of the main stream. CAs in S2 (Lanhe River) was the most prominent among all sample sites; the concentration of CAs was 190.8 µg/kg. The risk threshold of CAs in the sediment was calculated using the Equilibrium Partitioning approach (EqP), based on the distribution coefficient (Kp) and the predicted no-effect concentration (PNEC) in the water, and the values were 0.091-1.44 mg/kg. Based on the risk threshold, the ecological risk of the CAs in sediment was assessed using risk quotients (RQ). The results showed that the Chloramphenicol (CHL) was the most prominent in the Fenhe River Basin, and the proportion of medium-risk areas reached 21.7%, while all the other areas showed low risk. Secondly, the proportion of medium-risk areas was 17.4% for THI, and all the other areas showed low risk. The risk for Florfenicol (FF) was least among all CAs, and the proportion of low-risk areas was only 8.7%, while all the other areas were of insignificant risk.

10.
J Cancer Res Clin Oncol ; 149(12): 10109-10117, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37264265

RESUMO

PURPOSE: In this study, we aimed to explore the potential significance of AR expression in HER2-positive breast cancer patients who underwent neoadjuvant targeted therapy. Specifically, we investigated the correlation between AR expression levels and pathological complete response (pCR) rates. Our objective was to determine whether there were significant differences in pCR rates among HER2-positive breast cancer patients with different levels of AR expression. METHODS: We conducted a retrospective analysis of 258 HER-2 positive breast cancer patients who underwent neoadjuvant dual-blocked standard therapy (following the NCCN Guideline 2021) at three breast cancer centers in southwest China. We analyzed the clinicopathological features and pCR rates of these patients. The cut-off value for AR expression level was calculated as the median value of 70%. We used the chi-square test to investigate the correlation between AR expression level and pCR rate, as well as other clinicopathological features. RESULTS: Out of the 258 patients analyzed, 154 (59.69%) achieved pCR. Based on the cut-off value of 70%, AR expression level was classified as low (AR ≤ 70%) or high (AR > 70%) expression. Our analysis revealed a significant correlation between AR expression level and pCR rate in HER2-positive breast cancer patients (P = 0.031). We also found a significant association between pCR rate and clinical stage (P = 0.033) and chemotherapy regimen (P = 0.034). Furthermore, subgroup analyses showed that the pCR rate was higher in patients with high AR expression levels compared to those with low AR expression levels. Additionally, we observed that patients with an ER/AR ratio of less than 1 had a higher pCR rate than those with an ER/AR ratio greater than 1 (P = 0.038). CONCLUSION: Our study findings suggest that HER2-positive breast cancer patients with high AR expression levels may achieve higher pCR rates when treated with neoadjuvant dual-blocked therapy. Overall, our results support the idea that AR expression levels have a significant correlation with pCR rates in HER2-positive breast cancer patients receiving this particular form of treatment.


Assuntos
Neoplasias da Mama , Receptores Androgênicos , Feminino , Humanos , Androgênios , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Estudos Retrospectivos
11.
Environ Sci Pollut Res Int ; 30(26): 69683-69696, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37140859

RESUMO

Non-point source (NPS) pollution has always been the focus of research worldwide, and understanding the migration process is the basis for effective control of NPS pollution. In this study, the SWAT model and digital filtering algorithm were combined to explore the contribution of NPS pollution that migrated with underground runoff (UR) process to the Xiangxi River watershed. The results showed that the surface runoff (SR) was the main migration process of NPS pollution, while the contribution of NPS pollution that migrated with the UR process only accounted for 30.9%. With the decrease in annual precipitation among the three selected hydrological years, the proportion of NPS pollution that migrated with the UR process for TN decreased, whereas the proportion for TP increased. The contribution of NPS pollution migrated with UR process varied remarkably during different months. Although the maximum total load and the load of NPS pollution that migrated with the UR process for TN and TP all appeared in the wet season, due to the hysteresis effect, the load of NPS pollution that migrated with the UR process for TP appeared 1 month later than the total load of NPS pollution. With an increase in precipitation from the dry season to the wet season, the proportion of NPS pollution that migrated with the UR process for TN and TP decreased gradually, and the degree of decrease in NPS pollution that migrated with the UR process for TP was more evident than that for TN. Besides, being affected by topography, land use, and other factors, the proportion of NPS pollution that migrated with the UR process for TN decreased from 80% in upstream areas to 9% in downstream areas, while that for TP reached a maximum of 20% in downstream areas. Based on the research results, the contribution of soil and groundwater cumulative nitrogen and phosphorus should be considered, and different managements and control measures for different migration routes should be adopted in controlling pollution.


Assuntos
Poluição Difusa , Poluentes Químicos da Água , Poluição Difusa/análise , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Poluição Ambiental , Nitrogênio/análise , Fósforo/análise , Algoritmos , China
12.
iScience ; 26(4): 106495, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37096038

RESUMO

Chemerin, an adipocyte-secreted protein, has been recently suggested to be linked to metabolic syndrome and cardiac function in obese and diabetes mellitus. This study aimed to investigate the potential roles of adipokine chemerin on high fat-induced cardiac dysfunction. Chemerin (Rarres2) knockout mice, which were fed with either a normal diet or a high-fat diet for 20 weeks, were employed to observe whether adipokine chemerin affected lipid metabolism, inflammation, and cardiac function. Firstly, we found normal metabolic substrate inflexibility and cardiac function in Rarres2 -/- mice with a normal diet. Notably, in a high-fat diet, Rarres2 -/- mice showed lipotoxicity, insulin resistance, and inflammation, thus causing metabolic substrate inflexibility and cardiac dysfunction. Furthermore, by using in vitro model of lipid-overload cardiomyocytes, we found chemerin supplementation reversed the lipid-induced abnormalities above. Herein, in the presence of obesity, adipocyte-derived chemerin might function as an endogenous cardioprotective factor against obese-related cardiomyopathy.

13.
Environ Monit Assess ; 195(4): 455, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36892619

RESUMO

Inter-basin water transfer (IBWT) projects have been widely constructed to alleviate the pressure on water resources in water shortage basins. However, the ecological effects of IBWT projects have often been ignored. Based on the Soil and Water Assessment Tool (SWAT) model and a constructed total ecosystem services (TES) index, the impacts of IBWT projects on recipient basin ecosystem services were analyzed in this study. The results showed that the TES index was relatively stable from 2010 to 2020, but in the wet season it was 1.36 times that of the other months with high water yield and nutrient loads. Spatially, areas with high index values were mainly distributed in the sub-basins around the reservoirs. The IBWT projects had positive impacts on ecosystem services, and the TES index with IBWT projects was 5.98% higher than that without projects. Water yield and total nitrogen were the two most affected indexes, with increased of 5.65% and 5.41%, respectively, under the impacts of IBWT projects. Seasonally, the change rates of the TES index were less than 3% while the change rates of water yield and nitrogen load peaked at 8.23% and 53.42%, respectively, in March, owing to the large amount of water released from the reservoirs. Areas affected by the three evaluated IBWT projects accounted for 61%, 18%, and 11% of the watershed, respectively. Under the impact of each project, the TES index generally increased, whereas the impact decreased as the distance from the inflow location increased. Intense changes in ecosystem services occurred in sub-basin 23, the sub-basin closest to an IBWT project, with water yield, water flow, and local climate regulation increasing the largest.


Assuntos
Ecossistema , Rios , Solo , Água , Monitoramento Ambiental , Nitrogênio/análise
14.
Skin Res Technol ; 29(1): e13269, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36704881

RESUMO

BACKGROUND: Acne is the eighth-most prevalent inflammatory skin disease with no optimal treatment. Photodynamic therapy (PDT) is an effective treatment for severe acne. AIMS: The effect of PDT on the composition and diversity of skin microflora in severe acne patients was studied. MATERIALS AND METHODS: A total of 18 patients with severe acne and 8 healthy individuals were selected for this study. Patients were treated with 5-aminolevulinic acid-mediated PDT once a week three times in total; the skin microbiome was measured by 16S ribosomal RNA gene sequencing before and after treatment (1 week after each PDT). RESULTS: The microflora composition was different between healthy controls and patients, and between patients before and after treatment. Alpha diversity indices were lower in patients than those in control. There were 15 bacterial genera with high relative abundance that had noticeable changes during treatment. At the genus level,particularly Cutibacterium acnes (C. acnes formerly Propionibacterium acnes), there was no statistically significant difference among different group. The abundances of Staphylococcus epidermidis and Staphylococcus aureus were low. DISCUSSION: The microbial composition is different between severe acne patients acne patients and healthy individuals. The therapeutic efficacy of severe acne treated with PDT is associated with the composition and diversity of skin microbiota. CONCLUSION: The skin microbial composition changes after PDT treatment. PDT is an effective method for the treatment of severe acne.


Assuntos
Acne Vulgar , Microbiota , Fotoquimioterapia , Humanos , Acne Vulgar/tratamento farmacológico , Pele/microbiologia , Ácido Aminolevulínico/uso terapêutico , Ácido Aminolevulínico/farmacologia , Propionibacterium acnes/genética , Fotoquimioterapia/efeitos adversos
15.
J Hazard Mater ; 447: 130811, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-36669413

RESUMO

Benzotriazole ultraviolet stabilizers (BUVSs) are widespread emerging pollutants, which can pose exposure risks to benthic organisms. However, the toxicity and mechanisms of BUVSs congeners in benthic clams are far from elucidated. In this study, Asian clams (Corbicula fluminea) were exposed to one of UV-234, UV-326, UV-329, or UV-P at environmentally relevant levels (0.1, 1, and 10 µg/L) for 21 days. Filtration rate (FR) was increased in clams exposed to all BUVSs and there were notable histopathologic changes, including irregular digestive lumen, lipid droplet vacuolation, and degraded epithelial cells. To determine the molecular underpinnings following BUVSs exposure, the transcriptome responses in digestive glands were compared. Differentially expressed genes shared among BUVSs treatments were associated with focal adhesion, TNF-α/NF-κB proinflammatory pathways, and apoptosis. Following this, biochemical analysis of biomarkers related to apoptosis were conducted to further validate response. Exposure to BUVSs inhibited anti-oxidant enzyme activity and induced oxidative stress. Heat shock proteins were also triggered with exposure, and there was an induction of caspase-3 and caspase-9 activity. Molecular responses were not identical in the digestive gland of C. fluminea when comparing responses to BUVSs; nevertheless conserved mechanism (impairment of the oxidative defense system, immune system disruption, and induction of apoptosis) among BUVSs congeners was noted. This study provides novel insight into the toxicity and hazards of BUVSs in benthic organisms.


Assuntos
Corbicula , Poluentes Químicos da Água , Animais , Antioxidantes/metabolismo , Corbicula/metabolismo , Estresse Oxidativo , Toxicogenética , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismo
16.
Oral Dis ; 29(4): 1668-1679, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35255186

RESUMO

Long non-coding RNAs (lncRNAs) are thought to play important roles in non-syndromic orofacial clefts (NSOFC). Clinical diagnosis was categorized as either non-syndromic cleft lip with or without cleft palate (NSCL/P), or non-syndromic cleft palate only (NSCPO). Tissues excised from the trimmed wound edge were reserved as experimental samples; adjacent normal control was used as a positive control, and tissue from healthy individuals was used as a blank control. Target lncRNAs in the collected tissues were identified using microarrays and quantitative reverse transcription PCR (RT-qPCR). Immunohistochemical (IHC) staining and RT-qPCR were used to verify the target mRNAs. Pathway, gene ontology (GO) enrichment, and TargetScan predictions were employed to construct competing endogenous RNA networks (ceRNA networks) and explore their potential functions. RNA-Seq revealed 24 upregulated and 43 downregulated lncRNAs; MALAT1 and NEAT1 were screened and validated using RT-qPCR. Common NSOFC risk factors were positively correlated with MALAT1 and NEAT1 expression. Bioinformatics predicted four ceRNA networks; GO enrichment focused on their potential functions. RT-qPCR and IHC data were consistent with respect to expression levels of proteins and the mRNAs that encode them. As MALAT1 and NEAT1 are associated with the severity of NSOFC, they represent potential therapeutic targets and prognostic biomarkers.


Assuntos
Fenda Labial , Fissura Palatina , MicroRNAs , RNA Longo não Codificante , Humanos , Fenda Labial/genética , Fissura Palatina/genética , RNA Longo não Codificante/genética , Fatores de Risco , MicroRNAs/genética
17.
Environ Sci Pollut Res Int ; 30(8): 20402-20414, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36258113

RESUMO

As one of the important components of hydrological cycle, evapotranspiration spatial distribution is of great significance to regional water resources planning and rational utilization. This research used Surface Energy Balance System model to estimate the daily evapotranspiration (ET) in Beijing based on Landsat 8 observations. Results showed that the daily ET in Beijing ranged from 3.469 to 5.474 mm/day. ET is known to decrease with the increase of land surface temperature (LST) and to increase with the increase of Normalized Difference Vegetation Index (NDVI). NDVI primarily decreased from the northwest to the southeast. When the NDVI value was 0.4-0.6, the average ET peaked at 4.88 mm/day, and then slightly decreased by 3.7%. The coefficient of determination of NDVI (0.95) was much greater than that of LST (0.30) upon linear fitting, showing LST was not the main factor controlling ET in Beijing. In contrast to the linear fitting results, the spatial correlation between LST and ET is more significant than that between NDVI and ET in the global bivariate spatial analysis, where the absolute value of global bivariate Moran's I of LST (0.51) was higher than that of NDVI (0.21) at a resolution of 150 m. And the univariate spatial autocorrelation indices of LST, ET, and NDVI equaled 0.84, 0.65, and 0.51, respectively. Furthermore, the complex spatial distribution pattern of variables could significantly affect the correlation analysis results. Local bivariate spatial analysis showed that over 60% of the Beijing area had a significant correlation, of which the negative correlation area of LST accounted for about 85%, and the positive correlation area of NDVI accounted for 74%. By improving the correlation analysis accuracy, the regional conditions for the establishment of correlation analysis results were clarified from the overall correlation analysis results.


Assuntos
Clima , Monitoramento Ambiental , Monitoramento Ambiental/métodos , Temperatura , Análise Espacial
18.
J Stomatol Oral Maxillofac Surg ; 124(2): 101326, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36336299

RESUMO

Due to site-specific anatomical challenges, traditional immediate dental implant placement for mandibular multirooted molar sizes has many limitations. This technical report describes a modified approach for immediate dental implant placement in molar sites allowing for precise three-dimensional (3D) implant position and favourable clinical effect with the aid of a dynamic guidance system and flapless pre-extractive preparation of the implant bed.


Assuntos
Implantes Dentários , Humanos , Extração Dentária , Dente Molar/cirurgia
19.
Environ Toxicol Chem ; 42(1): 191-204, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36342347

RESUMO

Deriving water quality benchmarks based on the species sensitivity distribution (SSD) is crucial for assessing the ecological risks of antibiotics. The application of extrapolation methods such as interspecies correlation estimation (ICE) and acute-to-chronic ratios (ACRs) can effectively supplement insufficient toxicity data for these emerging contaminants. Acute-to-chronic ratios can predict chronic toxicity from acute toxicity, and ICE can extrapolate an acute toxicity value from one species to another species. The present study explored the impact of two extrapolation methods on the reliability of SSDs by analyzing different scenarios. The results show that, compared with the normal and Weibull distributions, the logistic model was the best-fitting model. For most antibiotics, SSDs derived by extrapolation have high reliability, with 82.9% of R2 values being higher than 0.9, and combining ICE and ACR methods can bring a maximum increase of 10% in R2 . Based on the results of Monte Carlo simulation, the statistical uncertainty brought by ICE in SSD is 10-40 times larger than that brought by ACR, and combining the two methods could reduce uncertainty. In addition, the sensitivity test showed that whether the toxicity data came from extrapolation or actual measurement, the lower the value of toxicity endpoints was, the greater the bias caused by the corresponding species in every scenario. Combining the two aforementioned extrapolation methods could effectively increase the stability of SSD, with their bias nearly equal to 1. Environ Toxicol Chem 2023;42:191-204. © 2022 SETAC.


Assuntos
Poluentes Químicos da Água , Qualidade da Água , Poluentes Químicos da Água/toxicidade , Antibacterianos/toxicidade , Reprodutibilidade dos Testes , Incerteza , Especificidade da Espécie , Medição de Risco
20.
Int J Mol Sci ; 25(1)2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38203302

RESUMO

Delta-like non-canonical Notch ligand 1 (DLK1), which inhibits the differentiation of precursor adipocytes, is a recognized marker gene for precursor adipocytes. Lipids play a crucial role in energy storage and metabolism as a vital determinant of beef quality. In this study, we investigated the mechanism of the DLK1 gene in lipid metabolism by constructing adipose tissue-specific knockout mice. We examined some phenotypic traits, including body weight, liver coefficient, fat index, the content of triglyceride (TG) and cholesterol (CHOL) in abdominal white adipose tissue (WAT) and blood. Subsequently, the fatty acid content and genes related to lipid metabolism expression were detected in DLK1-/- and wild-type mice via GC-MS/MS analysis and quantitative real-time PCR (qRT-PCR), respectively. The results illustrated that DLK1-/- mice exhibited significant abdominal fat deposition compared to wild-type mice. HE staining and immunohistochemistry (IHC) results showed that the white adipocytes of DLK1-/- mice were larger, and the protein expression level of DLK1-/- was significantly lower. Regarding the blood biochemical parameters of female mice, DLK1-/- mice had a strikingly higher triglyceride content (p < 0.001). The fatty acid content in DLK1-/- mice was generally reduced. There was a significant reduction in the expression levels of the majority of genes that play a crucial role in lipid metabolism. This study reveals the molecular regulatory mechanism of fat metabolism in mice and provides a molecular basis and reference for the future application of the DLK1 gene in the breeding of beef cattle with an excellent meat quality traits. It also provides a molecular basis for unravelling the complex and subtle relationship between adipose tissue and health.


Assuntos
Metabolismo dos Lipídeos , Espectrometria de Massas em Tandem , Feminino , Bovinos , Animais , Camundongos , Camundongos Knockout , Metabolismo dos Lipídeos/genética , Ligantes , Tecido Adiposo , Adipócitos Brancos , Ácidos Graxos , Triglicerídeos
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