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1.
Biomed Pharmacother ; 159: 114298, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36706633

RESUMO

Inflammatory bowel disease (IBD) results from a complex interplay between genetic predisposition, environmental factors, and gut microbes. The role of N6-methyladenosine (m6A) methylation in the pathogenesis of IBD has attracted increasing attention. m6A modification not only regulates intestinal mucosal immunity and intestinal barrier function, but also affects apoptosis and autophagy in intestinal epithelial cells. Additionally, m6A modification participated in the interaction between gut microbes and the host, providing a novel direction to explore the molecular mechanisms of IBD and the theoretical basis for specific microorganism-oriented prevention and treatment measures. m6A regulators are expected to be biomarkers for predicting the prognosis of IBD patients. m6A methylation may be utilized as a novel target in the management of IBD. This review focused on the recent advances in how m6A modification causes the initiation and development of IBD, and provided new insights into optimal prevention and treatment measures for IBD.

2.
Sci Rep ; 13(1): 1451, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36702865

RESUMO

Large-scale urban growth has modified the hydrological cycle of our cities, causing greater and faster runoff. Urban forests (UF), i.e. the stock of trees and shrubs, can substantially reduce runoff; still, how climate, tree functional types influence rainfall partitioning into uptake and runoff is mostly unknown. We analyzed 92 published studies to investigate: interception (I), transpiration (T), soil infiltration (IR) and the subsequent reduction in runoff. Trees showed the best runoff protection compared to other land uses. Within functional types, conifers provided better protection on an annual scale through higher I and T but broadleaved species provided better IR. Regarding tree traits, leaf area index (LAI) showed a positive influence for both I and T. For every unit of LAI increment, additional 5% rainfall partition through T (3%) and I (2%) can be predicted. Overall, runoff was significantly lower under mixed species stands. Increase of conifer stock to 30% in climate zones with significant winter precipitation and to 20% in areas of no dry season can reduce runoff to an additional 4%. The study presented an overview of UF potential to partition rainfall, which might help to select species and land uses in different climate zones for better storm-water management.

3.
Phytopathology ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36657140

RESUMO

Canker and dieback are serious fungal diseases of woody plants, which can cause huge economic losses to orchards. The purpose of this study was to classify and assess pathogenicity of fungal species associated with canker and dieback on fruit trees growing in Henan Province, China. In total, 150 isolates of Botryosphaeriaceae were obtained from six different fruit trees exhibiting typical symptoms of stem canker, branch dieback, and gummosis. Morphological examinations and phylogenetic analysis of ITS, tef1, tub2, and rpb2 revealed two Botryosphaeriaceae species, which are Botryosphaeria dothidea and a novel species, Lasiodiplodia regiae, respectively. Using Koch's postulates, we confirmed that the different isolates of L. regiae can cause disease in their original hosts. The pathogenicity tests showed that L. regiae can cause canker, dieback, and gummosis symptoms in four different hosts, indicating a relatively wider host range. Moreover, 10 L. regiae isolates exhibited similar symptoms but different levels of virulence on shoots of peach trees under field conditions. This study demonstrated that L. regiae was a new causal agent of canker and dieback of six fruit tree species, which could be a serious risk to the orchard industry in China. Furthermore, the findings also provided a foundation for further epidemiological studies and the development of management strategies.

4.
Cell Rep Med ; : 100911, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36657446

RESUMO

Predicting the clinical response to chemotherapeutic or targeted treatment in patients with locally advanced or metastatic lung cancer requires an accurate and affordable tool. Tumor organoids are a potential approach in precision medicine for predicting the clinical response to treatment. However, their clinical application in lung cancer has rarely been reported because of the difficulty in generating pure tumor organoids. In this study, we have generated 214 cancer organoids from 107 patients, of which 212 are lung cancer organoids (LCOs), primarily derived from malignant serous effusions. LCO-based drug sensitivity tests (LCO-DSTs) for chemotherapy and targeted therapy have been performed in a real-world study to predict the clinical response to the respective treatment. LCO-DSTs accurately predict the clinical response to treatment in this cohort of patients with advanced lung cancer. In conclusion, LCO-DST is a promising precision medicine tool in treating of advanced lung cancer.

5.
Plant Cell Environ ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658747

RESUMO

Hydrogen sulfide (H2 S) is considered to mediate plant growth and development. However, whether H2 S regulates the adaptation of mangrove plant to intertidal flooding habitats is not well understood. In this study, sodium hydrosulfide (NaHS) was used as an H2 S donor to investigate the effect of H2 S on the responses of mangrove plant Avicennia marina to waterlogging. The results showed that 24-h waterlogging increased reactive oxygen species (ROS) and cell death in roots. Excessive mitochondrial ROS accumulation is highly oxidative and leads to mitochondrial structural and functional damage. However, the application of NaHS counteracted the oxidative damage caused by waterlogging. The mitochondrial ROS production was reduced by H2 S through increasing the expressions of the alternative oxidase genes and increasing the proportion of alternative respiratory pathway in the total mitochondrial respiration. Secondly, H2 S enhanced the capacity of the antioxidant system. Meanwhile, H2 S induced Ca2+ influx and activated the expression of intracellular Ca2+ -sensing-related genes. In addition, the alleviating effect of H2 S on waterlogging can be reversed by Ca2+ chelator and Ca2+ channel blockers. In conclusion, this study provides the first evidence to explain the role of H2 S in waterlogging adaptation in mangrove plants from the mitochondrial aspect. This article is protected by copyright. All rights reserved.

6.
ACS Nano ; 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36661565

RESUMO

Although various artificial dyes and pigments have been invented, certain application fields need structural colors because they can last for centuries even under harsh conditions. Here, we report that the antireflective Ag brochosomes (soccer-ball-like microscale granules covered by nanobowls) become colorful when the nanobowls on the Ag brochosomes are filled by polystyrene (PS) nanospheres. The color originates from the enhanced electromagnetic resonances of the PS nanospheres by the surrounding metallic nanobowls, suggested by both the experimental and the simulation results. The color is determined by the size of the PS nanospheres. We can tailor the color simply by reducing the diameter of the PS nanospheres via the plasma etching treatment. The color intensity of the Ag brochosomes filled with PS nanospheres shows weak dependence on the observing angles, benefiting from their spherical shape. Plasma etching treatment of the Ag brochosomes filled with PS nanospheres through different masks can design various structural color patterns. The simple fabrication process and the easy processability make the Ag brochosomes filled with PS nanospheres have promising applications in the structural color fields.

7.
Nat Commun ; 14(1): 261, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650148

RESUMO

Separation of actinides from lanthanides is of great importance for the safe management of nuclear waste and sustainable development of nuclear energy, but it represents a huge challenge due to the chemical complexity of these f-elements. Herein, we report an efficient separation strategy based on ion sieving in graphene oxide membrane. In the presence of a strong oxidizing reagent, the actinides (U, Np, Pu, Am) in a nitric acid solution exist in the high valent and linear dioxo form of actinyl ions while the lanthanides (Ce, Nd, Eu, Gd, etc.) remain as trivalent/tetravalent spheric ions. A task-specific graphene oxide membrane with an interlayer nanochannel spacing between the sizes of hydrated actinyl ions and lanthanides ions is tailored and used as an ionic cut-off filter, which blocks the larger and linear actinyl ions but allows the smaller and spheric lanthanides ions to penetrate through, affording lanthanides/actinides separation factors up to ~400. This work realizes the group separation of actinides from lanthanides under highly acidic conditions by a simple ion sieving strategy and highlights the great potential of utilizing graphene oxide membrane for nuclear waste treatment.

8.
Comput Struct Biotechnol J ; 21: 665-676, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36659929

RESUMO

Endothelial cells (ECs) play an important role in tumor progression. Currently, the main target of anti-angiogenic therapy is the vascular endothelial growth factor (VEGF) pathway. Some patients do benefit from anti-VEGF/VEGFR therapy; however, a large number of patients do not have response or acquire drug resistance after treatment. Moreover, anti-VEGF/VEGFR therapy may lead to nephrotoxicity and cardiovascular-related side effects due to its action on normal ECs. Therefore, it is necessary to identify targets that are specific to tumor ECs and could be applied to various cancer types. We integrated single-cell RNA sequencing data from six cancer types and constructed a multi-cancer EC atlas to decode the characteristic of tumor ECs. We found that tip-like ECs mainly exist in tumor tissues but barely exist in normal tissues. Tip-like ECs are involved in the promotion of tumor angiogenesis and inhibition on anti-tumor immune responses. Moreover, tumor cells, myeloid cells, and pericytes are the main sources of pro-angiogenic factors. High proportion of tip-like ECs is associated with poor prognosis in multiple cancer types. We also identified that prostate-specific membrane antigen (PSMA) is a specific marker for tip-like ECs in all the cancer types we studied. In summary, we demonstrate that tip-like ECs are the main differential EC subcluster between tumors and normal tissues. Tip-like ECs may promote tumor progression through promoting angiogenesis while inhibiting anti-tumor immune responses. PSMA was a specific marker for tip-like ECs, which could be used as a potential target for the diagnosis and treatment of non-prostate cancers.

9.
Injury ; 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36669944

RESUMO

BACKGROUND: Reconstruction and repair of multiple defects in the hand is a combination of function, sensation and aesthetics. The reconstruction using the superficial circumflex iliac artery perforator flap has become popular, which overcomes the inherent shortcomings of traditional inguinal flaps by preserving the deep fascia. In this report, we present our experience in the design and clinical application of the superficial circumflex iliac artery perforator flap, which we used to repair multiple defects in the hand. METHODS: From January 2015 to December 2020, 41 patients received free superficial circumflex iliac artery perforator flap to repair multiple hand defects. All flaps were carefully designed according to the hand defect including 21 single and 20 bilobed flaps. The area of ​​the donor area is 2.5 cm × 3.0cm∼8.0 cm × 6.5 cm. We followed up all patients regularly and completed standardized assessments of outcomes based on post-reconstruction hand function and esthetic scores. RESULTS: 41 cases of flaps survived completely.3 cases of vascular crisis was relieved after surgical exploration, 1 case of mild distal necrosis was healed after dressing change, 1 case of pigmentation happened. There were 41 patients, 27 males and 14 females, with an average age of 40.5 years (4 to 59 years old). The defects included 20 cases opisthenars and 21 cases palms. The wounds were irregular, with exposed or damaged tendons, nerves or bones. All flaps were followed for a mean of 10.5 months (3 to 15 months). The functional and esthetic outcomes were satisfactory for all flaps without complications such as hand spasms, adhesions and scar contractures CONCLUSION: The superficial circumflex iliac artery perforator flap's donor site was concealed, relatively stable perforators, easy dissection. Recipient site condition was good and acceptable for the patients. It is a significant choice for multiple hand defects.

10.
Biology (Basel) ; 12(1)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36671793

RESUMO

Global cerebral ischemia can elicit rapid innate neuroprotective mechanisms that protect against delayed neuronal death. Brain-derived 17ß-estradiol (BDE2), an endogenous neuroprotectant, is synthesized from testosterone by the enzyme aromatase (Aro) and is upregulated by brain ischemia and inflammation. Our recent study revealed that G1, a specific G-protein-coupled estrogen receptor 1 (GPER) agonist, exerts anti-inflammatory and anti-apoptotic roles after global cerebral ischemia (GCI). Herein, we aimed to elucidate whether G1 modulates the early inflammatory process and the potential underlying mechanisms in the ovariectomized rat hippocampal CA1 region. G1 was found to markedly reduce pro-inflammatory (iNOS, MHCII, and CD68) and to enhance anti-inflammatory (CD206, Arginase 1, IL1RA, PPARγ, and BDNF) markers after 1 and 3 days of reperfusion after GCI. Intriguingly, the neuroprotection of G1 was blocked by the Aro inhibitor, letrozole. Conversely, the GPER antagonist, G36, inhibited Aro-BDE2 signaling and exacerbated neuronal damage. As a whole, this work demonstrates a novel anti-inflammatory role of GPER, involving a synergistic mediation with BDE2 during the early stage of GCI.

11.
Ecotoxicol Environ Saf ; 251: 114540, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36640570

RESUMO

Pesticides could induce long-term impacts on aquatic ecosystem via transgenerational toxicity. However, for many chiral pesticides, the potential enantioselectivity of transgenerational toxicity has yet to be fully understood. In this study, we used zebrafish as models to evaluate the maternal transfer risk of tebuconazole (TEB), which is a chiral triazole fungicide currently used worldwide and has been frequently detected in surface waters. After 28-day food exposure (20 and 400 ng/g) to the two enantiomers of TEB (S- and R-TEB) in adult female zebrafish (F0), increased malformation rate and decreased swimming speed were found in F1 larvae, with R-TEB showing higher impacts than S-enantiomer. Additionally, enantioselective effects on the secretion of thyroid hormones (THs) and expression of TH-related key genes along the hypothalamic-pituitary-thyroid (HPT) axis were found in both F0 and F1 after maternal exposure. Both the two enantiomers significantly disrupted the triiodothyronine (T3) and thyroxine (T4) contents in F0 with different degrees, whereas in F1, significant effects were only found in R-TEB groups with decreasing of both T3 and T4 contents. Most of the HPT axis related genes in F0 were upregulated by TEB and more sensitive to R-TEB than to S-TEB. In contrast, most of the genes in F1 were downregulated by both R- and S-TEB, especially the genes that are primarily responsible for thyroid development and growth (Nkx2-1), TH synthesis (NIS and TSHꞵ) and metabolism (Deio1). Findings from this study highlight the key role of enantioselectivity in the ecological risk assessment of chiral pesticides through maternal transfer.

12.
Sensors (Basel) ; 23(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36679769

RESUMO

Specular Reflections often exist in the endoscopic image, which not only hurts many computer vision algorithms but also seriously interferes with the observation and judgment of the surgeon. The information behind the recovery specular reflection areas is a necessary pre-processing step in medical image analysis and application. The existing highlight detection method is usually only suitable for medium-brightness images. The existing highlight removal method is only applicable to images without large specular regions, when dealing with high-resolution medical images with complex texture information, not only does it have a poor recovery effect, but the algorithm operation efficiency is also low. To overcome these limitations, this paper proposes a specular reflection detection and removal method for endoscopic images based on brightness classification. It can effectively detect the specular regions in endoscopic images of different brightness and can improve the operating efficiency of the algorithm while restoring the texture structure information of the high-resolution image. In addition to achieving image brightness classification and enhancing the brightness component of low-brightness images, this method also includes two new steps: In the highlight detection phase, the adaptive threshold function that changes with the brightness of the image is used to detect absolute highlights. During the highlight recovery phase, the priority function of the exemplar-based image inpainting algorithm was modified to ensure reasonable and correct repairs. At the same time, local priority computing and adaptive local search strategies were used to improve algorithm efficiency and reduce error matching. The experimental results show that compared with the other state-of-the-art, our method shows better performance in terms of qualitative and quantitative evaluations, and the algorithm efficiency is greatly improved when processing high-resolution endoscopy images.


Assuntos
Algoritmos , Endoscopia , Processamento de Imagem Assistida por Computador/métodos
13.
J Digit Imaging ; 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596937

RESUMO

Novel coronavirus disease 2019 (COVID-19) has rapidly spread throughout the world; however, it is difficult for clinicians to make early diagnoses. This study is to evaluate the feasibility of using deep learning (DL) models to identify asymptomatic COVID-19 patients based on chest CT images. In this retrospective study, six DL models (Xception, NASNet, ResNet, EfficientNet, ViT, and Swin), based on convolutional neural networks (CNNs) or transformer architectures, were trained to identify asymptomatic patients with COVID-19 on chest CT images. Data from Yangzhou were randomly split into a training set (n = 2140) and an internal-validation set (n = 360). Data from Suzhou was the external-test set (n = 200). Model performance was assessed by the metrics accuracy, recall, and specificity and was compared with the assessments of two radiologists. A total of 2700 chest CT images were collected in this study. In the validation dataset, the Swin model achieved the highest accuracy of 0.994, followed by the EfficientNet model (0.954). The recall and the precision of the Swin model were 0.989 and 1.000, respectively. In the test dataset, the Swin model was still the best and achieved the highest accuracy (0.980). All the DL models performed remarkably better than the two experts. Last, the time on the test set diagnosis spent by two experts-42 min, 17 s (junior); and 29 min, 43 s (senior)-was significantly higher than those of the DL models (all below 2 min). This study evaluated the feasibility of multiple DL models in distinguishing asymptomatic patients with COVID-19 from healthy subjects on chest CT images. It found that a transformer-based model, the Swin model, performed best.

15.
Artigo em Inglês | MEDLINE | ID: mdl-36646951

RESUMO

BACKGROUND: Immune checkpoint blockade (ICB) therapy can be effective against clear cell renal cell carcinoma (ccRCC), but many patients show no benefit. Tumor-derived pericytes (TDPs) may promote tumor progression by influencing T cells and are an immunotherapy target; however, they may comprise functionally distinct subtypes. We aimed to identify markers of tumor-promoting TDPs and develop TDP-targeting strategies to enhance ICB therapy effectiveness against ccRCC. METHODS: We analyzed the relationship between endosialin (EN) expression and cytotoxic T-lymphocyte (CTL) infiltration in ccRCC tumor samples using flow cytometry and in a ccRCC-bearing mice inhibited for EN via knockout or antibody-mediated blockade. The function of ENhigh TDPs in CTL infiltration and tumor progression was analyzed using RNA-sequencing (RNA-seq) data from ccRCC tissue-derived TDPs and single-cell RNA-seq (scRNA-seq) data from an online database. The role of EN in TDP proliferation and migration and in CTL infiltration was examined in vitro. Finally, we examined the anti-tumor effect of combined anti-EN and anti-programmed death 1 (PD-1) antibodies in ccRCC-bearing mice. RESULTS: High EN expression was associated with low CTL infiltration in ccRCC tissues, and inhibition of EN significantly increased CTL infiltration in ccRCC-bearing mice. RNA-seq and scRNA-seq analyses indicated that high EN expression represented the TDP activation state. EN promoted TDP proliferation and migration and impeded CTL infiltration in vitro. Finally, combined treatment with anti-EN and anti-PD-1 antibodies synergistically enhanced anti-tumor efficacy. CONCLUSION: ENhigh TDPs are in an activated state and inhibit CTL infiltration into ccRCC tissues. Combined treatment with anti-EN and anti-PD-1 antibodies may improve ICB therapy effectiveness against ccRCC.

16.
Cancers (Basel) ; 15(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36612298

RESUMO

MET inhibitors have shown promising efficacy for MET-dysregulated non-small cell lung cancer (NSCLC). However, quite a few patients cannot benefit from it due to the lack of powerful biomarkers. This study aims to explore the potential role of plasma proteomics-derived biomarkers for patients treated with MET inhibitors using mass spectrometry. We analyzed the plasma proteomics from patients with MET dysregulation (including MET amplification and MET overexpression) treated with MET inhibitors. Thirty-three MET-dysregulated NSCLC patients with longitudinal 89 plasma samples were included. We classified patients into the PD group and non-PD group based on clinical response. The baseline proteomic profiles of patients in the PD group were distinct from those in the non-PD group. Through protein screening, we found that a four-protein signature (MYH9, GNB1, ALOX12B, HSD17B4) could predict the efficacy of patients treated with MET inhibitors, with an area under the curve (AUC) of 0.93, better than conventional fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) tests. In addition, combining the four-protein signature with FISH or IHC test could also reach higher predictive performance. Further, the combined signature could predict progression-free survival for MET-dysregulated NSCLC (p < 0.001). We also validated the performance of the four-protein signature in another cohort of plasma using an enzyme-linked immunosorbent assay. In conclusion, the four plasma protein signature (MYH9, GNB1, ALOX12B, and HSD17B4 proteins) might play a substitutable or complementary role to conventional MET FISH or IHC tests. This exploration will help select patients who may benefit from MET inhibitors.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36634979

RESUMO

INTRODUCTION: Mutations of CEL gene were first reported to cause a new type of maturity-onset diabetes of the young (MODY) denoted as MODY8 and then were also found in patients with type 1 (T1D) and type 2 diabetes (T2D). However, its genotype-phenotype relationship has not been fully determined and how carboxyl ester lipase (CEL) variants result in diabetes remains unclear. The aim of our study was to identify pathogenic variants of CEL in patients with diabetes and confirm their pathogenicity. RESEARCH DESIGN AND METHODS: All five patients enrolled in our study were admitted to Shandong Provincial Hospital and diagnosed with diabetes in the past year. Whole-exome sequencing was performed to identify pathogenic variants in three patients with MODY-like diabetes, one newborn baby with T1D and one patient with atypical T2D, as well as their immediate family members. Then the consequences of the identified variants were predicted by bioinformatic analysis. Furthermore, pathogenic effects of two novel CEL variants were evaluated in HEK293 cells transfected with wild-type and mutant plasmids. Finally, we summarized all CEL gene variants recorded in Human Gene Mutation Database and analyzed the mutation distribution of CEL. RESULTS: Five novel heterozygous variants were identified in CEL gene and they were predicted to be pathogenic by bioinformatic analysis. Moreover, in vitro studies indicated that the expression of CELR540C was remarkably increased, while p.G729_T739del variant did not significantly affect the expression of CEL. Both novel variants obviously abrogated the secretion of CEL. Furthermore, we summarized all reported CEL variants and found that 74.3% of missense mutations were located in exons 1, 3, 4, 10 and 11 and most missense variants clustered near catalytic triad, Arg-83 and Arg-443. CONCLUSION: Our study identified five novel CEL variants in patients with different subtypes of diabetes, expanding the gene mutation spectrum of CEL and confirmed the pathogenicity of several novel variants.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Recém-Nascido , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Carboxilesterase/genética , Carboxilesterase/metabolismo , Células HEK293 , Lipase/genética , Lipase/metabolismo , Ésteres
18.
Nat Cell Biol ; 25(1): 79-91, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36536176

RESUMO

In eukaryotes, end-binding (EB) proteins serve as a hub for orchestrating microtubule dynamics and are essential for cellular dynamics and organelle movements. EB proteins modulate structural transitions at growing microtubule ends by recognizing and promoting an intermediate state generated during GTP hydrolysis. However, the molecular mechanisms and physiochemical properties of the EB1 interaction network remain elusive. Here we show that EB1 formed molecular condensates through liquid-liquid phase separation (LLPS) to constitute the microtubule plus-end machinery. EB1 LLPS is driven by multivalent interactions among different segments, which are modulated by charged residues in the linker region. Phase-separated EB1 provided a compartment for enriching tubulin dimers and other plus-end tracking proteins. Real-time imaging of chromosome segregation in HeLa cells expressing LLPS-deficient EB1 mutants revealed the importance of EB1 LLPS dynamics in mitotic chromosome movements. These findings demonstrate that EB1 forms a distinct physical and biochemical membraneless-organelle via multivalent interactions that guide microtubule dynamics.


Assuntos
Proteínas Associadas aos Microtúbulos , Microtúbulos , Humanos , Células HeLa , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Ligação Proteica , Tubulina (Proteína)/metabolismo
19.
Free Radic Biol Med ; 195: 132-144, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36584797

RESUMO

Tubulointerstitial fibrosis (TIF) is essential during the development of end-stage kidney disease (ESKD) and is associated with the impairment of fatty acid oxidation (FAO). Kruppel-like factor 14 (KLF14) is an important gene in lipid metabolism, but its role in TIF remains unknown. TGF-ß-stimulated HK-2 cells and mouse unilateral ureteral obstruction (UUO) were used as renal fibrosis models. The role of KLF14 in the process of renal fibrosis was verified by gene knockout mice, genetic or pharmacological interference in animal model and cell model respectively. In the current study, we found that KLF14 expression increased after activation of the TGF-ß signaling pathway during TIF. In KLF14-/- mice, more severe fibrosis was observed after unilateral ureteral obstruction (UUO) was induced. In human HK2 cells, knockdown of KLF14 led to more severe fibrosis induced by TGF-ß1, while overexpression of KLF14 partially attenuated this process. Specifically, KLF14 deficiency decreased mitochondrial FAO activity, resulting in lipid accumulation. Thus, the energy supply to the cells was insufficient, finally resulting in TIF. We further proved that KLF14 could target peroxisome proliferator activated receptor alpha (PPARα) as a transcriptional activator. This study identified the upregulation of KLF14 expression in response to kidney stress during the process of fibrosis. Upon TIF, the activated TGF-ß signaling pathway can enhance KLF14 expression, while the upregulation of KLF14 expression can decrease the degree of TIF by improving FAO activity in tubular epithelial cells and recovering the energy supply mediated by PPARα.


Assuntos
Nefropatias , Fatores de Transcrição Kruppel-Like , PPAR alfa , Obstrução Ureteral , Animais , Humanos , Camundongos , Ácidos Graxos/metabolismo , Fibrose , Rim/metabolismo , Nefropatias/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Metabolismo dos Lipídeos/genética , PPAR alfa/genética , PPAR alfa/metabolismo , Fator de Crescimento Transformador beta1/genética , Regulação para Cima , Obstrução Ureteral/genética , Camundongos Knockout
20.
Zhongguo Zhong Yao Za Zhi ; 47(22): 6020-6026, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36471925

RESUMO

Epimedii Folium is a well-known Chinese herbal medicine with the effect of nourishing kidney and strengthening Yang. Its main active ingredients are flavonoids. In this study, 60 samples of Epimedium sagittatum were collected for the determination of total flavonoids(TF) including the total amount of epimedin A, epimedin B, epimedin C, and icariin(abbreviated as ABCI) specified in the Chinese Pharmacopoeia as well as rhamnosylicariside Ⅱ and icariside Ⅱ. The calibration parameters of "first derivativemultiva-riate scattering correction in 1 900-650 cm~(-1) band(4-point smoothing)" and "first derivativestandard normal variable correction in 4 000-650 cm~(-1) full band(4-point smoothing)" were confirmed respectively. The quantitative model was established via Fourier infrared spectroscopy plus attenuated total reflection(FTIR-ATR) accessory combined with partial least squares(PLS) method and then used to predict the flavonoid content of 11 validation sets. The average prediction accuracy for ABCI in calibration set and validation set was 98.985% and 96.087%, respectively. The average prediction accuracy for TF in calibration set and validation set was 98.998% and 94.771%, respectively. These results indicated that FTIR-ATR combined with PLS model could be used for rapid prediction of flavonoid content in E. sagittatum, with the prediction accuracy above 94.7%. The establishment of this method provides a new solution for the detection of a large number of E. sagittatum samples.


Assuntos
Epimedium , Epimedium/química , Flavonoides/química , Folhas de Planta , Análise dos Mínimos Quadrados , Espectrofotometria Infravermelho
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