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1.
Bioorg Med Chem Lett ; 79: 129069, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36395995

RESUMO

In the present study, a series of cycloalkyl[b]thiophenylnicotinamide derivatives against α-glucosidase were synthesized, and evaluated for their in vitro and in vivo anti-diabetic potential. Most of the synthetic analogues exhibited superior α-glucosidase inhibitory effects than the standard drug acarbose (IC50 = 258.5 µM), in which compound 11b with cyclohexyl[b]thiophene core demonstrated the highest activity with an IC50 value of 9.9 µM and showed higher selectivity towards α-glucosidase over α-amylase by 7.4-fold. Fluorescence quenching experiment confirmed the direct binding of 11b with α-glucosidase, kinetics study revealed that 11b was a mixed-type inhibitor, and its binding mode was analyzed using molecular docking. Moreover, analogs compounds 6a-9b, 11b, 12b did not show in vitro cytotoxicity against LO2 and HepG2 cells. Finally, compound 11b exhibited in vivo hypoglycemic activity by reducing the blood glucose levels in sucrose-loaded rats.


Assuntos
Inibidores de Glicosídeo Hidrolases , alfa-Glucosidases , Animais , Ratos , Inibidores de Glicosídeo Hidrolases/farmacologia , Simulação de Acoplamento Molecular , Hipoglicemiantes/farmacologia , Acarbose
2.
J Affect Disord ; 320: 621-627, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36206885

RESUMO

BACKGROUND: Depressive symptoms and cognitive impairment are common psychiatric conditions and often co-occur in older adults. Network analysis has been widely used in exploring the inter-connections between psychiatric symptoms. The aim of this study was to explore the network model of depressive symptoms and cognitive performance, and their association with quality of life in people aged 65 years or above based on the 2017-2018 wave of Chinese Longitudinal Healthy Longevity Survey (CLHLS). METHOD: Global cognitive performance, depressive symptoms, and global quality of life (QoL) were measured using the validated Chinese version of the Mini Mental State Examination (MMSE), the 10-item Center for Epidemiologic Studies Short Depression Scale (CES-D), and the World Health Organization Quality of Life-brief version (WHOQOL-BREF), respectively. Central symptoms and bridge symptoms were identified via strength and bridge strength, respectively. The flow network was used to identify symptoms directly related to QoL. Network stability was examined using the case dropping bootstrap method. RESULTS: A total of 9023 participants were included in the network analysis. CESD3 "Feeling blue/depressed", CESD4 "Everything was an effort", and At_C "Attention and Calculation" were the central (influential) symptoms that had the highest strength value. Three bridge symptoms (i.e., Nam "Naming", CESD2 "Difficulty with concentrating", and Lan "Language") were also identified. CESD10 "Sleep disturbances" had the strongest direct connection to QoL. CONCLUSIONS: This exploratory study highlights the inter-relationships between cognitive performance and depressive symptoms in older adults in the general population. Interventions targeting bridge symptoms have the potential to alleviate depressive and cognitive symptoms in this population. Furthermore, improving sleep quality in older adults may reduce the negative impact of depression and cognition decline on QoL.


Assuntos
Disfunção Cognitiva , Qualidade de Vida , Humanos , Idoso , Qualidade de Vida/psicologia , Depressão/epidemiologia , Depressão/psicologia , Nível de Saúde , Disfunção Cognitiva/epidemiologia , Cognição , China/epidemiologia
3.
PLoS One ; 17(12): e0277906, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36454795

RESUMO

Facing increasingly severe environmental problems, as the largest developing country, achieving regional carbon emission reduction is the performance of China's fulfillment of the responsibility of a big government and the key to the smooth realization of the global carbon emission reduction goal. Since China's carbon emission data is updated slowly, in order to better formulate the corresponding emission reduction strategy, it is necessary to propose a more accurate carbon emission prediction model on the basis of fully analyzing the characteristics of carbon emissions at the provincial and regional levels. Given this, this paper first calculated the carbon emissions of eight economic regions in China from 2005 to 2019 according to relevant statistical data. Secondly, with the help of kernel density function, Theil index and decoupling index, the dynamic evolution characteristics of regional carbon emissions are discussed. Finally, an improved particle swarm optimization radial basis function (IPSO-RBF) neural network model is established to compare the simulation and prediction models of China's carbon emissions. The results show significant differences in carbon emissions in different regions, and the differences between high-value and low-value areas show an apparent expansion trend. The inter-regional carbon emission difference is the main factor in the overall carbon emission difference. The economic region in the middle Yellow River (ERMRYR) has the most considerable contribution to the national carbon emission difference, and the main contributors affecting the overall carbon emission difference in different regions are different. The number of regions with strong decoupling between carbon emissions and economic development is increasing in time series. The results of the carbon emission prediction model can be seen that IPSO-RBF neural network model optimizes the radial basis function (RBF) neural network, making the prediction result in a minor error and higher accuracy. Therefore, when exploring the path of carbon emission reduction in different regions in the future, the IPSO-RBF neural network model is more suitable for predicting carbon emissions and other relevant indicators, laying a foundation for putting forward more scientific and practical emission reduction plans.


Assuntos
Carbono , Desenvolvimento Econômico , Redes Neurais de Computação , China , Simulação por Computador
4.
Contact Dermatitis ; 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36461623

RESUMO

BACKGROUND: Chronic actinic dermatitis (CAD) is an immune-mediated photo-allergic skin disease. In the clinic, the treatment of this disease is hampered by the lack of proper understanding of the skin barrier dysfunction mechanism. OBJECTIVE: To illuminate the mechanism of skin barrier dysfunction in CAD. METHODS: Transcriptome sequencing and protein profiling were used to detect skin barrier injury-related genes. RNA pull down, a promoter-reporter gene assay, and chromatin isolation by RNA purification-sequencing were used to elucidate the effect of WAKMAR2 in skin barrier functionality. RESULTS: Transcriptome sequencing from patient's tissues showed a significantly decreased expression of WAKMAR2. Down-regulation of WAKMAR2 destroyed the keratinocyte barrier. Moreover, WAKMAR2 can directly bind to the c-Fos protein. This novel long non-coding RNA (LncRNA)-protein complexes were targeted to the CLDN1 promotor. Overexpression of WAKMAR2 enhanced the promoter activity of CLDN1, while the addition of AP-1 inhibitor could reverse this phenomenon. Furthermore, our in vivo results suggested that expression of WAKMAR2 was required for the repair of skin damage in mice induced by ultraviolet irradiation. CONCLUSIONS: We identified a crucial LncRNA (WAKMAR2) for the protection of the skin barrier in vitro and in vivo. Mechanically, it can specifically interact with c-Fos protein for the regulation of CLDN1, a finding which could be applied for CAD treatment.

5.
Front Public Health ; 10: 967693, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466507

RESUMO

Background: China is the only country in the world that has not included the Haemophilus influenzae type b (Hib) vaccine in its National Immunization Program, making it more difficult to eliminate Hib-related diseases through Hib vaccination. It is necessary to study parental preferences for Hib vaccination to optimize vaccine promotion strategies in China. Objective: This study aimed to investigate Chinese parental preference for five attributes of Hib vaccination, i.e., the place of origin, effectiveness, adverse event, doctors' recommendation, and the price of full vaccination when making a decision to vaccinate their children under 2 years old. Methods: A cross-sectional survey was conducted in two cities in Zhejiang Province from November to December in 2020 using a discrete choice experiment (DCE). A mixed logit model was used to estimate participating parents' preference for Hib vaccination attributes included in the DCE. Subgroup analysis and probability analysis were also conducted to capture the heterogeneity and trade-off of parental preference for Hib vaccination. Results: Data from 6,168 observations were included in the analyses. Parents of children are, on average, more likely to voice a positive preference for Hib vaccination. Such attributes of Hib vaccination as effectiveness and doctor's recommendation have a significant positive influence on parents' preference for Hib vaccination, while imported vaccines, adverse events, and the price of full vaccination have a significant negative influence on parents' preference. Parents with different demographic characteristics also existed heterogeneities in preference for Hib vaccination. Parents will make a trade-off on price if the Hib vaccine has a good performance on effectiveness and safety. Conclusion: The study found that, regardless of the place of origin of the Hib vaccine, parents with children under 2 years old prefer to compromise on price if the vaccine has a better effectiveness and safety profile. A proactive recommendation from doctors would strengthen their willingness for Hib vaccination. These findings help aid the development of communication strategies with parents for Hib vaccination in China.


Assuntos
Haemophilus influenzae tipo b , Criança , Humanos , Lactente , Estudos Transversais , Vacinação , Programas de Imunização , China
6.
Ann Transl Med ; 10(21): 1171, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36467343

RESUMO

Background: Cervical cancer patients have a high risk of metastasis and a poor prognosis with shorter disease-free survival. Thus, novel biomarkers and feasible therapies urgently need to be discovered. Previous studies have shown that miR-95-3p plays crucial roles in several cancer types. However, the roles of miR-95-3p in cervical cancer remain unknown. Methods: The micro ribonucleic acid (miRNA) expression data and clinical characteristics of cervical cancer samples were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were conducted to identify the prognostic-related miRNAs. The potential target genes of miR-95-3p were predicted by the TargetScan database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to explore the target gene of miR-95-3p. The effects of miR-95-3p inhibition and overexpression on cell proliferation were inspected by cell counting kit-8 (CCK-8) assays and cell colony formation assays. Wound-healing assays and transwell assays were also used to examine cell migration ability in HeLa and SiHa cells. Results: MiR-95-3p was the only miRNA significantly associated with the poor prognosis of cervical squamous cell carcinoma. A further analysis suggested that vascular cell adhesion molecule 1 (VCAM1) is a target gene of miR-95-3p in cervical cancer, and miR-95-3p promotes the malignant behavior of cervical cancer cells by inhibiting the expression of VCAM1. The CCK-8 and cell colony assays showed that miR-95-3p downregulation significantly suppressed cell proliferation in the HeLa and SiHa cells. The transwell and wound-healing assays showed that miR-95-3p inhibition suppressed cell migration in the HeLa and SiHa cells. Further the Western blot analysis and the quantitative real-time-polymerase chain reaction (qRT-PCR) showed that the knockdown of miR-95-3p in HeLa cells resulted in increased VCAM1 expression. And VCAM1 was highly expressed in the paired adjacent normal cervical epithelium tissue samples, but lowly expressed in the cervical tumor tissue samples. Conclusions: Our study was the first to show that miR-95-3p could serve as a prognostic biomarker of cervical cancer. Mechanistically, we discovered that miR-95-3p inhibited the expression of the cell adhesion molecule VCAM1 and thus promoted further tumor progression.

7.
Nat Prod Rep ; 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36472136

RESUMO

Covering: up to 2014-2022.Diterpenoid biosynthesis in plants builds on the necessary production of (E,E,E)-geranylgeranyl diphosphate (GGPP) for photosynthetic pigment production, with diterpenoid biosynthesis arising very early in land plant evolution, enabling stockpiling of the extensive arsenal of (di)terpenoid natural products currently observed in this kingdom. This review will build upon that previously published in the Annual Review of Plant Biology, with a stronger focus on enzyme structure-function relationships, as well as additional insights into the evolution of (di)terpenoid metabolism since generated.

8.
Medicine (Baltimore) ; 101(47): e31707, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36451388

RESUMO

To explore the risk factors for in-stent restenosis (ISR) after stent implantation in patients with coronary heart disease (CHD) using logistic regression analysis. From February 2020 to February 2022, 350 patients with CHD after percutaneous coronary intervention (PCI) were divided into a stent stenosis group and a stent nonstenosis group based on coronary angiography results performed 2 years after PCI. Univariate and multivariate logistic regressions were used to analyze the factors related to ISR after coronary stent implantation in patients with CHD. This study was approved by the Ethics Committee of Shandong University of Traditional Chinese Medicine. Patient signed informed consent. Of the 350 patients with CHD, 138 (39.43%) had stent restenosis while 212 did not. Univariate analysis showed that a family history of CHD, history of type 2 diabetes, hypertension, smoking, and drinking, discontinuation of aspirin, use of conventional dose statins, calcified lesions, ≥ 3 implanted stents, stent length ≥ 30 mm, stent diameter < 3 mm, and tandem stent increased the risk of restenosis. The incidence of restenosis was higher in the stent group than that in the nonstent group (P < .05). There were no significant differences in the blood lipid level, left ventricular ejection fraction, clopidogrel/ticagrelor or beta-blocker withdrawal, location of culprit vessels, and thrombotic lesions between the 2 groups (P > .05). Multivariate logistic regression analysis showed that family history of CHD, history of type 2 diabetes, hypertension, smoking, and drinking, aspirin withdrawal, use of conventional doses of statins, calcified lesions, ≥ 3 implanted stents, stent length ≥ 30 mm, stent diameter < 3 mm, and tandem stenting were risk factors for ISR within 2 years after PCI. A family history of CHD, history of type 2 diabetes, hypertension, smoking, and drinking, discontinuation of aspirin, use of conventional dose statins, calcified lesions, ≥ 3 stent implantations, stent length ≥ 30 mm, stent diameter < 3 mm, and tandem stenting are risk factors for ISR within 2 years after PCI in patients with CHD.


Assuntos
Doença da Artéria Coronariana , Reestenose Coronária , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipertensão , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/cirurgia , Constrição Patológica , Intervenção Coronária Percutânea/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Volume Sistólico , Reestenose Coronária/epidemiologia , Reestenose Coronária/etiologia , Função Ventricular Esquerda , Stents/efeitos adversos , Fatores de Risco , Aspirina/uso terapêutico
9.
Cell Death Discov ; 8(1): 464, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36424385

RESUMO

Highly specific and potent inhibitors of dihydroorotate dehydrogenase (DHODH), an essential enzyme of the de novo pyrimidine ribonucleotide synthesis pathway, are in clinical trials for autoimmune diseases, viral infections and cancer. However, because DHODH inhibitors (DHODHi) are immunosuppressants they may reduce the anticancer activity of the immune system. Therefore, there may be a need to improve the therapeutic index of DHODHi in cancer patients. The aim of this study was to find strategies to protect activated T cells from DHODHi and to identify cancer types hypersensitive to these inhibitors. First, we observed that like uridine supplementation, adding cytidine to the culture medium protects T cells from DHODH blockage. Next, we identified tumor types with altered expression of pyrimidine ribonucleotide synthesis enzymes. In this regard, we detected that the expression of cytidine deaminase (CDA), which converts cytidine into uridine, is low in an important proportion of cancer cell lines and consistently low in neuroblastoma samples and in cell lines from neuroblastoma and small cell lung carcinoma. This suggested that in the presence of a DHODHi, an excess of cytidine would be deleterious for low CDA expressing cancer cell lines. We show that this was the case (as could be seen almost immediately after treatment) when cells were cultured with fetal bovine serum but, was significantly less evident when cultures contained human serum. One interesting feature of CDA is that aside from acting intracellularly, it is also present in human plasma/serum. Altogether, experiments using recombinant CDA, human serum, pharmacologic inhibition of CDA and T cell/cancer cell co-cultures suggest that the therapeutic index of DHODHi could be improved by selecting patients with low-CDA expressing cancers in combination with strategies to increase cytidine or the cytidine/uridine ratio in the extracellular environment. Collectively, this proof-of-principle study warrants the discovery of agents to deplete extracellular CDA.

10.
Sci Total Environ ; 858(Pt 3): 160109, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36370777

RESUMO

Butyl benzyl phthalate (BBP), a typical phthalate plasticizer, is frequently detected in aquatic environments, but its possible effects on fish liver are unknown. In this study, adult zebrafish were exposed to 5-500 µg/L BBP and cultured for 28 days. The toxicity mechanism of environmentally relevant concentrations of BBP in the liver was explored using integrated biomarker response (IBR), molecular docking, and histopathological analysis, based on the tests of oxidative stress, apoptosis, and tissue damage, respectively. The results revealed that exposure to 500 µg/L BBP caused lipid peroxidation and DNA damage and induced inflammatory responses in the liver and intestinal tissues. The accumulation of reactive oxygen species (ROS) is the primary manifestation of BBP toxicity and is accompanied by changes in the activities of antioxidant and detoxification enzymes. Notably, the pro-apoptotic genes (p53 and caspase-3) were still significantly upregulated in the 50 µg/L and 500 µg/L treatment groups on day 28. Moreover, BBP interfered with apoptosis by forming a stable complex with apoptosis proteins (P53 and Caspase-3). Our findings are helpful for understanding the toxicity mechanisms of BBP, which could further promote the assessment of the potential environmental risks of BBP.

12.
Sci Adv ; 8(48): eadd3197, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36449622

RESUMO

Insulin and glucagon secreted from the pancreas with dynamic balance play a vital role in regulating blood glucose levels. Although distinct glucose-responsive insulin delivery systems have been developed, the lack of a self-regulated glucagon release module limits their clinical applications due to the potential risk of hypoglycemia. Here, we describe a transdermal polymeric microneedle patch for glucose-responsive closed-loop insulin and glucagon delivery to achieve glycemic regulation with minimized risk of hypoglycemia. The glucose-responsive phenylboronic acid units can bind to glucose to reversibly shift the net charge (from positive to negative) of the entire polymeric matrix within microneedles. Therefore, the release ratio of the negatively charged insulin and the positively charged glucagon analog from the patch can be dynamically tuned upon the fluctuation of blood glucose levels to realize glycemic homeostasis. In both chemically induced type 1 diabetic mouse and minipig models, this glucose-responsive dual-hormone microneedle patch demonstrated tight long-term regulation in blood glucose levels (>24 hours in minipigs).


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Suínos , Animais , Camundongos , Glucagon , Glucose , Glicemia , Insulina , Porco Miniatura , Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Infusão de Insulina , Polímeros
13.
Front Plant Sci ; 13: 1019512, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325560

RESUMO

Rhizoctonia solani Kühn naturally infects and causes Sheath blight disease in cereal crops such as wheat, rice and maize, leading to severe reduction in grain yield and quality. In this work, a new bacterial strain Bacillus halotolerans LDFZ001 showing efficient antagonistic activity against the pathogenic strain Rhizoctonia solani Kühn sh-1 was isolated. Antagonistic, phylogenetic and whole genome sequencing analyses demonstrate that Bacillus halotolerans LDFZ001 strongly suppressed the growth of Rhizoctonia solani Kühn sh-1, showed a close evolutionary relationship with B. halotolerans F41-3, and possessed a 3,965,118 bp circular chromosome. Bioinformatic analysis demonstrated that the genome of Bacillus halotolerans LDFZ001 contained ten secondary metabolite biosynthetic gene clusters (BGCs) encoding five non-ribosomal peptide synthases, two polyketide synthase, two terpene synthases and one bacteriocin synthase, and a new kijanimicin biosynthetic gene cluster which might be responsible for the biosynthesis of novel compounds. Gene-editing experiments revealed that functional expression of phosphopantetheinyl transferase (SFP) and major facilitator superfamily (MFS) transporter genes in Bacillus halotolerans LDFZ001 was essential for its antifungal activity against R. solani Kühn sh-1. Moreover, the existence of two identical chitosanases may also make contribution to the antipathogen activity of Bacillus halotolerans LDFZ001. Our findings will provide fundamental information for the identification and isolation of new sheath blight resistant genes and bacterial strains which have a great potential to be used for the production of bacterial control agents. Importance: A new Bacillus halotolerans strain Bacillus halotolerans LDFZ001 resistant to sheath blight in wheat is isolated. Bacillus halotolerans LDFZ001 harbors a new kijanimicin biosynthetic gene cluster, and the functional expression of SFP and MFS contribute to its antipathogen ability.

14.
Acta Biomater ; 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36328127

RESUMO

Transition-metal chalcogenides, such as noble metal chalcogenides, hold tremendous potential as efficient agents for photo-induced cancer theranostics due to their unique physicochemical properties. However, a critical bottleneck still lies in exploring simple and controllable methods to synthesize noble metal chalcogenides especially PtS for in vivo photo-induced cancer imaging and simultaneous therapy. Herein, we proposed the albumin-templated synthesis of size-controllable platinum (II) sulfide nanodots (PtS-NDs) for multimodal cancer imaging and potent photothermal therapy. PtS-NDs were precisely synthesized with a tunable size ranging from 2.1 nm to 4.5 nm through a thermodynamically controlled growth inside albumin nanocages. PtS-NDs yielded significant near-infrared (NIR) absorbance and outstanding photothermal conversion under NIR laser irradiation, as well as effective resistance to photobleaching, thereby generating remarkable in vivo photoacoustic signals and distinct hyperthermia at tumor site. Moreover, these nanodots possessed efficient cellular uptake and tumor targeting capabilities in a size-dependent manner, thus leading to controllable diagnostic and thermo-therapeutic efficacy. Specifically, PtS-NDs with core diameter of 4.5 nm displayed preferable in vivo photoacoustic and CT imaging with high sensitivity, spatially and anatomically enhanced imaging contrast, together with hyperthermia mediated tumor ablation. Thus, the albumin-templated biomimetic synthesis provided an insightful strategy on fabricating theranostic PtS-NDs for potential clinical applications. STATEMENT OF SIGNIFICANCE: Noble metal chalcogenides especially PtS are of particular importance in the field of precise nanomedicine to improve both accuracy of cancer diagnosis and efficiency of tumor treatment. However, the intensively preclinical investigation of PtS was limited due to the lack of simple and controllable synthetic methods. Here, we report an albumin-templated biomineralization synthesis of platinum (II) sulfide nanodots (PtS-NDs). Specifically, albumin-templated biomineralization of PtS-NDs was induced by the electrostatic interactions between albumin and Pt2+, followed by the nucleation and growth inside the albumin nanocages. The resulting PtS-NDs showed good dispersibility and biosafety, as well as size-dependent photophysical properties and biological behaviors. Therefore, albumin-based biomineralization is a promising and safe strategy to facilely fabricate Pt-based chalcogenide for tumor theranostics.

15.
Front Vet Sci ; 9: 995629, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439356

RESUMO

Background: Milk fat is one of the main reference elements for evaluating milk quality and is a primary objective trait in dairy cattle breeding. In recent years, circular RNAs (circRNAs) have been found to play crucial roles in many biological processes. However, the function and expression profiles of circRNAs in milk fat synthesis in cows are not completely understood. We performed RNA sequencing to analyze the genome-wide expression of circRNA transcripts in bovine mammary epithelial cells (BMECs) from cows with extreme differences in milk fat percentage. We identified candidate differential circRNAs associated with milk fat metabolism using functional enrichment analysis and constructed a lipid metabolism-related competing endogenous RNA (ceRNA) interactive regulatory network. Results: A total of 290 circRNAs were significantly differentially expressed (DE-circRNAs) in high milk fat percentage (HMF) cows compared to that in low milk fat percentage (LMF) cows. Of the 290 circRNAs, 142 were significantly upregulated and 148 were significantly downregulated. Enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) identified four DE-circRNAs (circ_0001122, circ_0007367, circ_0018269, and circ_0015179) that potentially regulate milk fat metabolism. Among them, circ_0001122, circ_0007367, and circ_0015179 had relatively high expression levels in cow mammary gland tissue compared to other tissues (heart, liver, kidney, uterus, ovaries, and small intestine) of cows. The regulatory networks circ_0001122:miR-12043:LIPG, circ_0007367:miR-331-3p:CIDEA/PML, and circ_0018269:miR-11989:RORC/HPX are potential networks to explore the mechanism of milk fat regulation. Conclusions: These results reveal the possible role of circRNAs in milk fat metabolism in dairy cows. Several important circRNAs and ceRNAs affecting milk fat synthesis were identified, providing insights into the complex biology of milk fat synthesis as well as a novel theoretical perspective for future research on lactation, milk quality, and breed improvement in dairy cows.

16.
Aesthet Surg J ; 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36441969

RESUMO

BACKGROUND: The septal extension graft (SEG) has become the preferred augmentation rhinoplasty technique in Asia for its superiority in correcting tip projection and rotation. OBJECTIVES: The author sought to build a rabbit model for SEG surgery and compared the postoperative stability of the tip support between the bilateral batten costal and conchal cartilage extension grafts at the nasal tip. METHODS: Twenty rabbits underwent SEG surgery with either bilateral batten costal cartilage graft (Group A) or bilateral batten conchal cartilage graft (Group B). Serial photographs were obtained to evaluate the change of the nasal tip shape and graft shape. The observed indices include tip projection, tip angle, shape of extension graft, and histological features of the extension graft. RESULTS: Twelve weeks after the operation, one costal extension graft in group A (1/10) and three conchal extension grafts in group B (3/10) were reabsorbed. The costal cartilage graft showed better exterior results than conchal cartilage graft in terms of tip projection and angle relapse rate (13.01% vs. 25.02% and 15.18% vs. 28.73%, p < 0.05). The costal cartilage graft maintains its structure more than the conchal cartilage graft. A greater degree of calcification and more fibrous capsules around the extension graft were found in Group A. CONCLUSIONS: A rhinoplasty rabbit model was established to compare costal and conchal autologous cartilages for SEG. Additionally, this model may serve as a training tool for rhinoplasty surgeons. The costal cartilage extension graft is more reliable in terms of stability and may be paid more attention.

17.
Neurosci Lett ; 793: 136976, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36427816

RESUMO

The inferior colliculus (IC) is the hub along the auditory pathway. Although it is fundamentally an auditory structure, the neurons in the IC, especially its non-lemniscal part also respond to multimodal stimuli. However, the sources of these non-auditory inputs are unclear. In this study, we injected the rAAV2-retro virus, a virus with efficient retrograde function, into the non-lemniscal IC of the Ai14 reporter line. The majority of cortical and subcortical brain areas, including cognitive, motor, somatosensory, auditory, and visual-related regions were revealed. The quantified whole brain input data have showed that the non-lemniscal IC received a higher proportion of inputs from ipsilateral cortical brain regions. The non-lemniscal IC integrates different multimodal patterns, for the dorsal cortex (ICD) receives primarily auditory inputs, and the external cortex (ICE) receives primarily auditory and somatosensory inputs. These findings demonstrate that auditory integration is shaped by a network of multi-sensory connections in the non-lemniscal IC subregions.

18.
Front Pharmacol ; 13: 968776, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339585

RESUMO

Background: Heterogeneous phenotypes that display distinct common characteristics of osteoarthritis (OA) are not well defined and will be helpful in identifying more customized therapeutic options for OA. Circular RNAs (circRNAs) have attracted more and more attention due to their role in the progression of OA. Investigating the role of circRNAs in the pathogenesis of OA will contribute to the phenotyping of OA and to individualized treatment. Methods: Small extracellular vesicles (sEV) were isolated from serum samples from patients with OA of different stages and sEV-derived circPARD3B was determined using RT-qPCR analysis. CircPARD3B expression in a stimulated coculture that included OA fibroblast-like synoviocytes (OA-FLS) as well as human dermal microvascular endothelial cells (HDMECs), plus the effects of circPARD3B on the expression of vascular endothelial growth factor (VEGF) long with angiogenic activity, were evaluated in vitro. Based on bioinformatics analysis and luciferase reporter assay (LRA), MiR-326 and sirtuin 1 (SIRT1) were found to be interactive partners of circPARD3B. Mesenchymal stem cells (SMSCs) overexpressing circPARD3B were constructed and SMSCs-derived sEV with overexpressed circPARD3B (OE-circPARD3B-SMSCs-sEV) were obtained to explore the effect of the intervention of circPARD3B combined with SMSCs-sEV-based therapy in vitro and in a OA model induced by collagenase in vivo. Results: Serum sEV-linked circPARD3B was indentified to be significantly decreased in the inflammatory phenotype of OA. Overexpression of circPARD3B was found to inhibit the expression of VEGF, as well as the angiogenesis induced by VEGF in a IL-1ß stimulated the co-culture of OA-FLS as well as HDMECs. CircPARD3B is directly bound to miR-326. SIRT1 was considered a novel miR-326 target gene. OE-circPARD3B-SMSCs-sEV significantly reduced VEGF expression in coculture of OA-FLS and HDMECs. Injection of OE-circPARD3B-SMSCs-sEV could also reduce synovial VEGF; additionally, it could further ameliorate OA in the mouse model of OA in vivo. Conclusion: Serum sEV circPARD3B is a potential biomarker that enables the identification of the inflammatory phenotype of patients with OA. Correspondingly, intracellular transfer of circPARD3B through OE-circPARD3B-SMSCs-sEV could postpone disease progression through a functional module regulated angiogenesis of circPARD3B-miR-326-SIRT1, providing a novel therapeutic strategy for OA.

19.
Front Pharmacol ; 13: 1039235, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408232

RESUMO

There are technical obstacles in the safety evaluation of traditional Chinese medicine (TCM) injections due to their complex chemical nature and the lack of rapid and accurate in vitro methods. Here, we established a dual in vitro mitochondrial toxicity approach combing the conventional "glucose/galactose" assay in HepG2 cells with the cytotoxic assay in mitochondrial respiration deficient cells. Using this dual in vitro approach, for the first time, we systematically assessed the mitochondrial toxicity of TCM injections. Four of the 35 TCM injections, including Xiyanping, Dengzhanhuasu, Shuanghuanglian, and Yinzhihuang, significantly reduced cellular ATP production in galactose medium in the first assay, and presented less cytotoxic in the respiration deficient cells in the second assay, indicating that they have mitochondrial toxicity. Furthermore, we identified scutellarin, rutin, phillyrin, and baicalin could be the potential mitochondrial toxic ingredients in the 4 TCM injections by combining molecular docking analysis with experimental validation. Collectively, the dual in vitro approach is worth applying to the safety evaluation of more TCM products, and mitochondrial toxic TCM injections and ingredients found in this study deserve more attention.

20.
Chem Sci ; 13(44): 13100-13109, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36425486

RESUMO

Forging carbon-carbon (C-C) linkage in DNA-encoded combinatorial library synthesis represents a fundamental task for drug discovery, especially with broad substrate scope and exquisite functional group tolerance. Here we reported the palladium-catalyzed Suzuki-Miyaura, Heck and Hiyama type cross-coupling via DNA-conjugated aryl diazonium intermediates for DNA-encoded chemical library (DEL) synthesis. Starting from commodity arylamines, this synthetic route facilely delivers vast chemical diversity at a mild temperature and pH, thus circumventing damage to fragile functional groups. Given its orthogonality with traditional aryl halide-based cross-coupling, the aryl diazonium-centered strategy expands the compatible synthesis of complex C-C bond-connected scaffolds. In addition, DNA-tethered pharmaceutical compounds (e.g., HDAC inhibitor) are constructed without decomposition of susceptible bioactive warheads (e.g., hydroxamic acid), emphasizing the superiority of the aryl diazonium-based approach. Together with the convenient transformation into an aryl azide photo-crosslinker, aryl diazonium's DNA-compatible diversification synergistically demonstrated its competence to create medicinally relevant combinatorial libraries and investigate protein-ligand interactions in pharmaceutical research.

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