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1.
Mol Biol Evol ; 40(1)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36625089

RESUMO

Determining the functional consequences of karyotypic changes is invariably challenging because evolution tends to obscure many of its own footprints, such as accumulated mutations, recombination events, and demographic perturbations. Here, we describe the assembly of a chromosome-level reference genome of the gayal (Bos frontalis) thereby revealing the structure, at base-pair-level resolution, of a telo/acrocentric-to-telo/acrocentric Robertsonian translocation (2;28) (T/A-to-T/A rob[2;28]). The absence of any reduction in the recombination rate or genetic introgression within the fusion region of gayal served to challenge the long-standing view of a role for fusion-induced meiotic dysfunction in speciation. The disproportionate increase noted in the distant interactions across pro-chr2 and pro-chr28, and the change in open-chromatin accessibility following rob(2;28), may, however, have led to the various gene expression irregularities observed in the gayal. Indeed, we found that many muscle-related genes, located synthetically on pro-chr2 and pro-chr28, exhibited significant changes in expression. This, combined with genome-scale structural variants and expression alterations in genes involved in myofibril composition, may have driven the rapid sarcomere adaptation of gayal to its rugged mountain habitat. Our findings not only suggest that large-scale chromosomal changes can lead to alterations in genome-level expression, thereby promoting both adaptation and speciation, but also illuminate novel avenues for studying the relationship between karyotype evolution and speciation.


Assuntos
Cromatina , Genoma , Animais , Bovinos
2.
Biosens Bioelectron ; 224: 115052, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36603285

RESUMO

Toxicity screening and risk assessment of an overwhelmingly large and ever-increasing number of chemicals are vitally essential for ecological safety and human health. Genotoxicity is particularly important because of its association with mutagenicity, carcinogenicity and cancer. Phosphorylated histone H2AX (γH2AX) is an early sensitive genotoxic biomarker. It is therefore highly desirable to develop analytical methods for the detection of trace γH2AX to enable screening and assessment of genotoxicity. Here, we developed a novel cathodic photoelectrochemical (PEC) immunoassay with dual signal amplification for the rapid and ultrasensitive detection of γH2AX in cell lysates. A sandwich immuno-reaction targeting γH2AX was first carried out on a 96-well plate, using a secondary antibody/gold nanoparticle/glucose oxidase conjugate as the labeled detection antibody. The conjugate increased the production of H2O2 and thus provided the first mechanism of signal amplification. The immuno-reaction product containing H2O2 was then detected on a photocathode prepared from Bi2+xWO6 rich in oxygen vacancies, with H2O2 acting as electron acceptor. The oxygen vacancies acted as both adsorption and activation sites of H2O2 and thus enhanced the photocurrent, which provided another mechanism of signal amplification. As a result, an ultrasensitive immunoassay for γH2AX determination was established with a limit of detection of 6.87 pg/mL (S/N = 3) and a wide linear range from 0.01 to 500 ng/mL. The practicability of this assay was verified by detecting γH2AX in cell lysates exposed to known genotoxic chemicals. Our work offers a promising tool for the screening of genotoxic chemicals and opening a new avenue toward environmental risk assessment.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Humanos , Peróxido de Hidrogênio , Ouro , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Biomarcadores , Dano ao DNA , Técnicas Eletroquímicas/métodos , Limite de Detecção
3.
Nano Lett ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36701555

RESUMO

The disorganized vasculatures in tumors represent a substantial challenge of intratumor nanomedicine delivery to exert the anticancer effects. Herein, we rationally designed a glutathione (GSH)-activated nitric oxide (NO) donor loaded bioinspired lipoprotein system (NO-BLP) to normalize tumor vessels and then promote the delivery efficiency of sequential albumin-bound paclitaxel nanoparticles (PAN) in tumors. NO-BLP exhibited higher tumor accumulation and deeper penetration versus the counterpart liposomal formulation (NO-Lipo) in 4T1 breast cancer tumors, thus producing notable vascular normalization efficacy and causing a 2.33-fold increase of PAN accumulation. The sequential strategy of NO-BLP plus PAN resulted in an 81.03% inhibition of tumor growth in 4T1 tumors, which was better than the NO-BLP monotherapy, PAN monotherapy, and the counterpart NO-Lipo plus PAN treatment. Therefore, the bioinspired lipoprotein of NO-BLP provides an encouraging platform to normalize tumor vessels and promote intratumor delivery of nanomedicines for effective cancer treatment.

5.
J Oncol ; 2023: 9315027, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36660243

RESUMO

An abnormality in the regulation of adenosine deaminase acting on RNA (ADAR) enzymes, which catalyzed adenosine-to-inosine (A-to-I) RNA editing, was closely associated with the highly aggressive biologic behavior and poor prognosis in many malignancies. In the present study, we aimed to investigate the relationship among transcript factors-microRNAs regulatory network, immune environment, and ADAR gene in colorectal carcinoma (CRC). The association among the expression levels of ADAR mRNA and copy number variation, methylation, and mutation status were comprehensively analyzed using cBioPortal, Wanderer, and UALCAN databases in CRC datasets. ADAR-transcript factors (TFs) and ADAR-miRNA regulation networks were constructed by Cistrome Cancer and miRWalk2.0, respectively. The full network and subnetworks for ADAR coexpression genes were constructed using the STRING database and visualized by the MCODE module of the Cytoscape app. The relationship between ADAR mRNA expression and the abundance of infiltrating immune cells in CRC patients was explored by the Tumor Immune Estimation Resource, CIBERSORT, and single-gene gene set enrichment analysis (GSEA). ADAR mRNA was elevated and was a cancer essential gene in CRC. ADAR mRNA and transcripts P110 were significantly elevated in CRC compared to normal controls. Low-level methylation in the promoter region and high copy number amplification of ADAR were responsible for high levels of ADAR mRNA expression. ADAR coexpression genes were mainly involved in immunoregulation, especially T-lymphocyte activation. Hub genes, including CD2, CD274, and FASLG, were also significantly upregulated in the ADAR-high group compared to the control group. Besides, M1 macrophages were enriched in the ADAR-high group compared to the control group. This study demonstrated that ADAR, a new essential gene, was involved in the immune regulator and was a novel immune treatment target in CRC.

6.
Environ Sci Ecotechnol ; 14: 100232, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36685748

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) have become cause for growing concern in the Arctic ecosystems, partly due to their stable levels despite global emission reduction. Wildfire is considered one of the primary sources that influence PAH levels and trends in the Arctic, but quantitative investigations of this influence are still lacking. This study estimates the global emissions of benzo[a]pyrene (BaP), a congener of PAHs with high carcinogenicity, from forest and grassland fires from 2001 to 2020 and simulates the contributions of wildfire-induced BaP emissions from different source regions to BaP contamination in the Arctic. We find that global wildfires contributed 29.3% to annual averaging BaP concentrations in the Arctic from 2001 to 2020. Additionally, we show that wildfires contributed significantly to BaP concentrations in the Arctic after 2011, enhancing it from 10.1% in 2011 to 83.9% in 2020. Our results reveal that wildfires accounted for 94.2% and 50.8% of BaP levels in the Asian Arctic during boreal summer and autumn, respectively, and 74.2% and 14.5% in the North American Arctic for the same seasons. The source-tagging approach identified that local wildfire biomass emissions were the largest source of BaP in the Arctic, accounting for 65.7% of its concentration, followed by those of Northern Asia (17.8%) and Northern North America (13.7%). Our findings anticipate wildfires to play a larger role in Arctic PAH contaminations alongside continually decreasing anthropogenic emissions and climate warming in the future.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36674371

RESUMO

Understanding the specific effects of multidimensional elements of a built environment, transportation management policies, and the socio-demographics of travelers associated with commuting carbon emissions is significant for planners in promoting low-carbon and healthy urban development through transportation and land use and urban management policies. Most of the existing studies focus on the complex mechanisms affecting commuting behavior, but the relevant elements and specific mechanisms affecting commuting carbon emissions have not received sufficient attention. This study uses a random forest approach to analyze residential travel data from Wuhan, China. The results show that built environment and transportation demand management policies are critical to commuting carbon emissions, and that there is a non-linear association between multidimensional factors and commuting carbon emissions in Chinese cities. In addition, the study examines the synergistic effects of built environment and transportation management policies on commuting carbon emissions among different built environment elements. The results of the study provide valuable insights for planners in formulating low-carbon city and transportation development policies.


Assuntos
Carbono , Meios de Transporte , Cidades , Carbono/análise , China , Viagem
8.
Math Biosci Eng ; 20(1): 1297-1316, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36650812

RESUMO

BACKGROUND: Automatic liver segmentation is a prerequisite for hepatoma treatment; however, the low accuracy and stability hinder its clinical application. To alleviate this limitation, we deeply mine the context information of different scales and combine it with deep supervision to improve the accuracy of liver segmentation in this paper. METHODS: We proposed a new network called MAD-UNet for automatic liver segmentation from CT. It is grounded in the 3D UNet and leverages multi-scale attention and deep supervision mechanisms. In the encoder, the downsampling pooling in 3D UNet is replaced by convolution to alleviate the loss of feature information. Meanwhile, the residual module is introduced to avoid gradient vanishment. Besides, we use the long-short skip connections (LSSC) to replace the ordinary skip connections to preserve more edge detail. In the decoder, the features of different scales are aggregated, and the attention module is employed to capture the spatial context information. Moreover, we utilized the deep supervision mechanism to improve the learning ability on deep and shallow information. RESULTS: We evaluated the proposed method on three public datasets, including, LiTS17, SLiver07, and 3DIRCADb, and obtained Dice scores of 0.9727, 0.9752, and 0.9691 for liver segmentation, respectively, which outperform the other state-of-the-art (SOTA) methods. CONCLUSIONS: Both qualitative and quantitative experimental results demonstrate that the proposed method can make full use of the feature information of different stages while enhancing spatial data's learning ability, thereby achieving high liver segmentation accuracy. Thus, it proved to be a promising tool for automatic liver segmentation in clinical assistance.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Pessoal de Saúde , Tomografia Computadorizada por Raios X , Processamento de Imagem Assistida por Computador
9.
Sci Adv ; 9(2): eabo7605, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36630508

RESUMO

Execution of lineage-specific differentiation programs requires tight coordination between many regulators including Ten-eleven translocation (TET) family enzymes, catalyzing 5-methylcytosine oxidation in DNA. Here, by using Keratin 14-Cre-driven ablation of Tet genes in skin epithelial cells, we demonstrate that ablation of Tet2/Tet3 results in marked alterations of hair shape and length followed by hair loss. We show that, through DNA demethylation, Tet2/Tet3 control chromatin accessibility and Dlx3 binding and promoter activity of the Krt25 and Krt28 genes regulating hair shape, as well as regulate interactions between the Krt28 gene promoter and distal enhancer. Moreover, Tet2/Tet3 also control three-dimensional chromatin topology in Keratin type I/II gene loci via DNA methylation-independent mechanisms. These data demonstrate the essential roles for Tet2/3 in establishment of lineage-specific gene expression program and control of Dlx3/Krt25/Krt28 axis in hair follicle epithelial cells and implicate modulation of DNA methylation as a novel approach for hair growth control.


Assuntos
Cromatina , Dioxigenases , Cromatina/genética , Dioxigenases/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Diferenciação Celular/genética , Metilação de DNA
10.
Nat Commun ; 14(1): 194, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635324

RESUMO

Non-specific phospholipase C (NPC) hydrolyzes major membrane phospholipids to release diacylglycerol (DAG), a potent lipid-derived messenger regulating cell functions. Despite extensive studies on NPCs reveal their fundamental roles in plant growth and development, the mechanistic understanding of phospholipid-hydrolyzing by NPCs, remains largely unknown. Here we report the crystal structure of Arabidopsis NPC4 at a resolution of 2.1 Å. NPC4 is divided into a phosphoesterase domain (PD) and a C-terminal domain (CTD), and is structurally distinct from other characterized phospholipases. The previously uncharacterized CTD is indispensable for the full activity of NPC4. Mechanistically, CTD contributes NPC4 activity mainly via CTDα1-PD interaction, which ultimately stabilizes the catalytic pocket in PD. Together with a series of structure-guided biochemical studies, our work elucidates the structural basis and provides molecular mechanism of phospholipid hydrolysis by NPC4, and adds new insights into the members of phospholipase family.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fosfolipases Tipo C , Proteínas de Arabidopsis/fisiologia , Hidrólise , Fosfolipídeos , Fosfolipases Tipo C/fisiologia
11.
Oncol Lett ; 25(1): 18, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36478904

RESUMO

Multiple primary cancers (MPCs) have an increasing incidence rate due to the detection of early stages of cancer and the development of effective therapeutic strategies. MPCs are less common compared with metachronous cancers. Therefore, distinguishing synchronous primary tumors from metastasis and developing an individualized treatment strategy can be challenging. In the present study, the case of a 70-year-old female who was referred to The First Hospital of Jilin University (Changchun, China) with an enlarged left cervical lymph node and no other clinical manifestations is reported. Radiography revealed distinct lesions in the left breast, left cervical lymph node and bilateral lungs. Subsequently, a biopsy was performed in all three lesions and then each specimen was subjected to immunohistochemistry, fluorescence in situ hybridization, amplification refractory mutation system-PCR and next-generation sequencing (NGS). Disease-related enrichment of lymph node mutant genes and Gene Ontology Biological Process enrichment of breast, as well as lung, mutant genes were performed using the Database for Annotation, Visualization and Integrated Discovery. Based on the molecular assessment, the patient was finally diagnosed with breast invasive ductal carcinoma, primary lung adenocarcinoma and cervical lymph node metastatic lung adenocarcinoma. Since primary synchronous breast and lung cancer (SBLC) is rare, a molecular assessment, particularly using NGS, could provide important information for both the diagnosis and treatment of SBLC.

12.
Bioresour Technol ; 370: 128534, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36574889

RESUMO

This work investigated the effect of calcium hypochlorite (CH) coupled aged refuse (AR) treatment on the enhanced hydrogen generation from sludge anaerobic dark fermentation (SADF). The enhanced mechanism was systematically revealed through sludge disintegration, organic matter biotransformation, and microbial community characteristics, etc. The experimental data showed that CH coupled AR increased the hydrogen yield to 18.1 mL/g, significantly higher than that in the AR or CH group alone. Mechanistic analysis showed that CH-coupled AR significantly promoted sludge disintegration and hydrolysis processes, providing sufficient material for hydrogen-producing bacteria. Microbiological analysis showed that CH-coupled AR increased the relative abundance of responsible hydrogen-producing microorganisms. In addition, CH-coupled AR was very effective in reducing phosphate content in the fermentation liquid and fecal coliforms in the digestate, thus facilitating the subsequent treatment of fermentation broth and digestate. CH coupled AR is an alternative strategy to increase hydrogen production from sludge.


Assuntos
Hidrogênio , Esgotos , Fermentação , Anaerobiose , Esgotos/microbiologia , Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Ácidos Graxos Voláteis/metabolismo
13.
Zhongguo Zhong Yao Za Zhi ; 47(22): 6127-6136, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36471937

RESUMO

To investigate the therapeutic effect of Jingfang Granules on carbon tetrachloride(CCl_4)-induced liver fibrosis in mice and its mechanism. Forty-nine 8-week-old male C57 BL/6 J mice were randomly divided into a blank group, a CCl_4 group, a silybin group(positive control, 100 mg·kg~(-1))+CCl_4, a Jingfang high-dose(16 g·kg~(-1)) group, a Jingfang high-dose(16 g·kg~(-1))+CCl_4 group, a Jingfang medium-dose(8 g·kg~(-1))+CCl_4 group, and a Jingfang low-dose(4 g·kg~(-1))+CCl_4 group, with 7 mice in each group. The mice in the blank group and Jingfang high-dose group were intraperitoneally injected olive oil solution, and mice in other groups were intraperitoneally injected with 10% CCl_4 olive oil solution(5 mL·kg~(-1)) to induce liver fibrosis, twice a week with an interval of 3 d, for 8 weeks. At the same time, except for the blank group and CCl_4 group, which were given deionized water, the mice in other groups were given the corresponding dose of drugs by gavage once daily for 8 weeks with the gavage volume of 10 mL·kg~(-1). All mice were fasted and freely drank for 12 h after the last administration, and then the eyeballs were removed for blood collection. The liver and spleen were collected, and the organ index was calculated. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bile acid(TBA), and triglyceride(TG) in the serum of mice were detected by an automated analyzer. Tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and interleukin-1ß(IL-1ß) levels were detected by enzyme-linked immunosorbent assay(ELISA). Kits were used to detect the contents of superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the liver tissue. Pathological changes in the liver tissue were observed by hematoxylin-eosin(HE), Masson, and Sirius red staining. Western blot was used to detect protein expressions of transforming growth factor-ß(TGF-ß), α-smooth muscle actin(α-SMA) and Smad4 in the liver tissue. The results indicated that Jingfang Granules significantly reduced the organ index, levels of ALT, AST, TBA,TG, TNF-α, IL-6, and IL-1ß in the serum, and the content of MDA in the liver tissue of mice with CCl_4-induced liver fibrosis. Jingfang Granules also significantly increased the content of SOD and GSH in the liver tissue. Meanwhile, Jingfang Granules down-regulated the protein levels of TGF-ß, α-SMA, and Smad4. Furthermore, Jingfang Granules had no significant effect on the liver tissue morphology and the above indexes in the normal mice. In conclusion, Jingfang Granules has obvious therapeutic effect on CCl_4-induced liver fibrosis, and its mechanism may be related to reducing the expression of pro-inflammatory factors, anti-oxidation, and regulating TGF-ß/Smad4 signaling pathway.


Assuntos
Interleucina-6 , Fator de Necrose Tumoral alfa , Camundongos , Masculino , Animais , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Azeite de Oliva/metabolismo , Azeite de Oliva/farmacologia , Azeite de Oliva/uso terapêutico , Tetracloreto de Carbono/efeitos adversos , Tetracloreto de Carbono/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Fígado , Superóxido Dismutase/metabolismo , Fator de Crescimento Transformador beta/metabolismo
14.
Zhongguo Zhong Yao Za Zhi ; 47(20): 5467-5472, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36471961

RESUMO

This study explored the curative effect of Jingfang Mixture on urticaria mice induced by aluminum hydroxide/ovalbumin, and discussed its mechanism. Sixty male Kunming mice were randomly divided into a normal group, a model group, three Jingfang Mixture(low-dose, medium-dose, and high-dose) groups, and a positive drug(cetirizine hydrochloride) group. The urticarial model in mice was induced by the intraperitoneal injection of the mixed solution of ovalbumin and aluminum hydroxide. The degrees of pruritus were observed after the second immunization. Pathological changes were detected by hematoxylin and eosin(HE) staining. Levels of interleukin 1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in the serum were detected by enzyme linked immunosorbent assay(ELISA). Expressions of NOD-like receptor protein 3(NLRP3) and IL-1ß were detected by immunohistochemistry(IHC). Expressions of nuclear factor kappa-B(NF-κB p65), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate-specific proteases 1(caspase-1), and IL-1ß proteins were detected by Western blot. The results showed that, except for the normal group, the mice in all groups had different degrees of pruritus. Compared with the model group, the Jingfang Mixture groups and the positive drug group prolonged the scratching latency of mice(P<0.05), and significantly reduced the number of scratching(P<0.05). In addition, the Jingfang Mixture groups and the positive drug group improved the pathological morphology of skin tissue. The expression levels of IL-1ß and TNF-α in serum were significantly reduced(P<0.05), and the number of NLRP3 and IL-1ß positive cells was decreased(P<0.01). The expressions of p-NF-κB p65, NLRP3, ASC, cleaved caspase-1, and IL-1ß protein were significantly down-regulated(P<0.05). The results of the above study indicate that Jingfang Mixture inhibit the inflammatory response in urticaria mice, and the mechanism may be related to the inhibition of activating NF-κB/NLRP3/IL-1ß signaling pathway.


Assuntos
NF-kappa B , Urticária , Animais , Masculino , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ovalbumina , Hidróxido de Alumínio/farmacologia , Transdução de Sinais , Caspase 1/genética , Caspase 1/metabolismo , Prurido
15.
Zhongguo Zhong Yao Za Zhi ; 47(20): 5488-5493, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36471964

RESUMO

This study aims to clarify the effect of Jingfang Mixture on the treatment of chronic urticarial and its mechanism, and investigate the regulatory effect of chronic urticaria on the metabolic disorder of endogenous metabolites in the blood. The mice were randomly divided into normal group, model group, and Jingfang Mixture group, and modeling and administration continued for 21 d. The changes in endogenous small molecules in rat serum were determined by ultra-high performance liquid chromatography-electrospray ionization-Q Exactive-Orbitrap-mass spectrometry(UHPLC-ESI-QE-Orbitrap-MS) metabolomics technology. The change trend of endogenous metabolites in rat serum was analyzed to find potential biomarkers. The results showed that Jingfang Mixture regulate 16 biomarkers, mainly including taurine, glutamate, succinic acid, docosahexaenoic acid, and arachidonic acid. Metabolic pathway analysis was carried out by MetaboAnalyst, and P<0.01 was taken as the potential key metabolic pathway. Ten metabolic pathways were closely related to the treatment of chronic urticarial by Jingfang Mixture, mainly involved in the glutamate metabolism, taurine and hypotaurine metabolism, arginine and proline metabolism, arachidonic acid metabolism, tricarboxylic acid cycle, unsaturated fatty acid biosynthesis, glutathione metabolism, phenylalanine metabolism, alanine, aspartic acid, and glutamate metabolism, and butyric acid metabolism. Glutamate metabolism and butyric acid metabolism involved more metabolic pathways than others. Therefore, it was speculated that Jingfang Mixture had a balanced regulating effect on the related metabolic pathways which caused the serum disorder in the rats with urticaria, and tended to regulate the metabolic differential to the normal level in the rats with urticaria. This paper provides references for studying the mechanism of Jingfang Mixture from the perspective of endogenous metabolites and metabolic pathways in vivo. At the same time, the endogenous substances explored in this paper can be used as important biomarkers for the prevention of urticaria.


Assuntos
Urticária Crônica , Ratos , Camundongos , Animais , Ácido Araquidônico , Ácido Butírico , Metabolômica/métodos , Cromatografia Líquida de Alta Pressão/métodos , Biomarcadores/metabolismo , Taurina , Glutamatos
16.
BMC Health Serv Res ; 22(1): 1483, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36474239

RESUMO

BACKGROUND: Inadequate preoperative management of chronic medications can place perioperative patients at risk and cause unnecessary delays in surgical procedures. This study aims to investigate the prevalence of chronic medication therapy problems (CMTPs) in hospitalized perioperative patients and assess the relevance of pharmacists' interventions. METHODS: We conducted a retrospective study of pharmacist-led preoperative management of chronic medications in hospitalized adult patients from November 2018 to April 2019. The recorded drug-related problems (DRPs) were retrospectively reviewed and categorized according to the Pharmaceutical Care Network Europe classification V9.1 and were analyzed with a multinomial regression model to identify risk factors. RESULTS: A total of 254 DRPs were recorded, with an average of 0.52 DRPs per patient. Treatment safety (66.9%) was the most common DRP. The most frequent causes of perioperative DRPs and nonperioperative DRPs were drug selection (72.9%) and patient related (50.8%), respectively. Of the 292 documented interventions, 71.6% were fully accepted by the clinicians and patients. The majority (68.9%) of the recorded problems were completely resolved. The number of comorbidities (OR = 3.815) and the number of chronic medications taken (OR = 1.539) were risk factors for the occurrence of DRPs. CONCLUSION: The findings of this study suggest that pharmacist-led chronic medication therapy management in surgical wards may be an effective method to help reduce medication-related surgical risks and optimize the medication therapies used for the long-term treatment of chronic diseases.

17.
Biomater Sci ; 2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36475528

RESUMO

High-quality postoperative rehabilitation is the focus of most patients currently, and hypertrophic scar (HS) greatly reduces the patient's quality of life due to the symptom of severe itching. Traditional HS therapies are associated with limitations, such as poor drug delivery efficiency for topical administration and severe pain for intralesional injection. In this study, we developed a personalized microneedle patch system for minimally invasive and effective treatment of HSs. The microneedle patches were personalized designed and fabricated with 3D printing in order to adapt to individual HS. The optimized microneedle patches were composed of dissolving gelatin and starch and loaded with losartan. Losartan, as a drug class of angiotensin II receptor blockers (ARBs), can effectively inhibit the proliferation and migration of hypertrophic scar fibroblasts (HSFs) and downregulate the gene expression related to scar formation in HSFs. The dissolving microneedle patches exhibited strong mechanical strength, effectively penetrated the stratum corneum of HSs and increased the losartan delivery into HSs upon dissolution of gelatin and starch. Together, the losartan-loaded microneedle patches effectively inhibited the formation of HSs in rabbit ears with reduced scar elevation index (SEI), and decreased fibrosis and collagen deposition in HSs. This personalized microneedle patch system increases the drug delivery efficiency into HSs with minimal invasion, and opens a new window for personalized management and treatment of skin diseases.

18.
Animals (Basel) ; 12(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36552449

RESUMO

GPX2 has been recognized as a potential candidate gene for feed efficiency in pigs. This article aimed to elucidate polymorphism of GPX2 associated with feed efficiency and its related molecular mechanism. In this study, seven single nucleotide polymorphisms (SNP) of GPX2 were found among 383 Duroc pigs. In addition, seven SNPs and ALGA0043483 (PorcineSNP60 BeadChip data in 600 Duroc pigs), which are near the GPX2 gene, were identified in one haplotypes block. Furthermore, associated studies showed that the genotype of GPX2 has significant association with weaning weight and 100 kg BF in Duroc pigs. In addition, the AG had no effect when the backfat became thinner, and the FCR and RFI traits had a tendency to decrease in the G3 + TT combination genotype, accompanied by an increase of GPX2 expression in backfat and muscle tissues. At the cellular level, the adipocyte proliferation and ability of adipogenic differentiation were reduced, and the lipid degradation increased in 3T3-L1 when there was overexpression of GPX2. In contrast, overexpression of the GPX2 gene can promote the muscle cell proliferation and myogenic differentiation in C2C12 cells. In other words, GPX2 has the effect of reducing fat deposition and promoting muscle development, and it is a candidate gene for backfat and feed efficiency.

19.
Front Plant Sci ; 13: 1065766, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36479520

RESUMO

Flowering time is strongly related to the environment, while the genotype-by-environment interaction study for flowering time is lacking in Brassica napus. Here, a total of 11,700,689 single nucleotide polymorphisms in 490 B. napus accessions were used to associate with the flowering time and related climatic index in eight environments using a compressed variance-component mixed model, 3VmrMLM. As a result, 19 stable main-effect quantitative trait nucleotides (QTNs) and 32 QTN-by-environment interactions (QEIs) for flowering time were detected. Four windows of daily average temperature and precipitation were found to be climatic factors highly correlated with flowering time. Ten main-effect QTNs were found to be associated with these flowering-time-related climatic indexes. Using differentially expressed gene (DEG) analysis in semi-winter and spring oilseed rapes, 5,850 and 5,511 DEGs were found to be significantly expressed before and after vernalization. Twelve and 14 DEGs, including 7 and 9 known homologs in Arabidopsis, were found to be candidate genes for stable QTNs and QEIs for flowering time, respectively. Five DEGs were found to be candidate genes for main-effect QTNs for flowering-time-related climatic index. These candidate genes, such as BnaFLCs, BnaFTs, BnaA02.VIN3, and BnaC09.PRR7, were further validated by the haplotype, selective sweep, and co-expression networks analysis. The candidate genes identified in this study will be helpful to breed B. napus varieties adapted to particular environments with optimized flowering time.

20.
Mar Pollut Bull ; 187: 114500, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36586200

RESUMO

This study provides a comprehensive compilation of published toxicological and environmental data further used to assess the ecological risks of six antifouling biocides, including tributyltin (TBT), Irgarol 1051, Diuron, Chlorothalonil, 4,5-Dichloro-N-octyl-3(2H)-isothiazolone (DCOIT), and Dichlofluanid. The standard maximum concentration and standard continuous concentration of antifouling biocides were derived by the species susceptibility distribution method. Following that, the ecological risk assessment of antifouling biocides in the aquatic environment was conducted using the hazard quotient, margin of safety, joint probability curve, and Monte Carlo random sampling method. The following is a concise list of the antifouling biocide dangers associated with acute and chronic risks: Irgarol 1051 > TBT > Diuron > DCOIT > Chlorothalonil > Dichlofluanid. It is strongly advised that systematic and ongoing monitoring of these biocides in coastal areas take place, as well as the creation of acceptable and efficient environmental protection measures, to safeguard the coastal environment's services and functions.

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