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1.
World J Clin Cases ; 12(16): 2862-2868, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38899292

RESUMEN

BACKGROUND: Rectal mucosal melanoma is a rare and highly aggressive disease. Common symptoms include anal pain, an anal mass, or bleeding. As such, the disease is usually detected on rectal examination of patients with other suspected anorectal diseases. However, due to its rarity and nonspecific symptoms, melanoma of the rectal mucosa is easily misdiagnosed. CASE SUMMARY: This report describes the case of a 58-year-old female patient who presented with a history of blood in her stool for the prior one or two months, without any identifiable cause. During colonoscopy, a bulge of approximately 2.2 cm × 2.0 cm was identified. Subsequently, the patient underwent endoscopic ultrasound (EUS) to characterize the depth of invasion of the lesions. EUS suggested a hypoechoic mucosal mass with involvement of the submucosal layer and heterogeneity of the internal echoes. Following surgical intervention, the excised tissue samples were examined and confirmed to be rectal malignant melanoma. The patient recovered well with no evidence of recurrence during follow-up. CONCLUSION: This case shows that colonoscopy with EUS and pathological examination can accurately diagnose rare cases of rectal mucosal melanoma.

2.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(3): 487-494, 2024 Jun 18.
Artículo en Chino | MEDLINE | ID: mdl-38864135

RESUMEN

OBJECTIVE: To unveil the pathological changes associated with demyelination in schizophrenia (SZ) and its consequential impact on interstitial fluid (ISF) drainage, and to investigate the therapeutic efficacy of ursolic acid (UA) in treating demyelination and the ensuing abnormalities in ISF drainage in SZ. METHODS: Female C57BL/6J mice, aged 6-8 weeks and weighing (20±2) g, were randomly divided into three groups: control, SZ model, and UA treatment. The control group received intraperitoneal injection (ip) of physiological saline and intragastric administration (ig) of 1% carboxymethylcellulose sodium (CMC-Na). The SZ model group was subjected to ip injection of 2 mg/kg dizocilpine maleate (MK-801) and ig administration of 1% CMC-Na. The UA treatment group underwent ig administration of 25 mg/kg UA and ip injection of 2 mg/kg MK-801. The treatment group received UA pretreatment via ig administration for one week, followed by a two-week drug intervention for all the three groups. Behavioral assessments, including the open field test and prepulse inhibition experiment, were conducted post-modeling. Subsequently, changes in the ISF partition drainage were investigated through fluorescent tracer injection into specific brain regions. Immunofluorescence analysis was employed to examine alterations in aquaporin 4 (AQP4) polarity distribution in the brain and changes in protein expression. Myelin reflex imaging using Laser Scanning Confocal Microscopy (LSCM) was utilized to study modifications in myelin within the mouse brain. Quantitative data underwent one-way ANOVA, followed by TukeyHSD for post hoc pairwise comparisons between the groups. RESULTS: The open field test revealed a significantly longer total distance [(7 949.39±1 140.55) cm vs. (2 831.01±1 212.72) cm, P < 0.001] and increased central area duration [(88.43±22.06) s vs. (56.85±18.58) s, P=0.011] for the SZ model group compared with the controls. The UA treatment group exhibited signifi-cantly reduced total distance [(2 415.80±646.95) cm vs. (7 949.39±1 140.55) cm, P < 0.001] and increased central area duration [(54.78±11.66) s vs. (88.43±22.06) s, P=0.007] compared with the model group. Prepulse inhibition test results demonstrated a markedly lower inhibition rate of the startle reflex in the model group relative to the controls (P < 0.001 for both), with the treatment group displaying significant improvement (P < 0.001 for both). Myelin sheath analysis indicated significant demyelination in the model group, while UA treatment reversed this effect. Fluorescence tracing exhibited a significantly larger tracer diffusion area towards the rostral cortex and reflux area towards the caudal thalamus in the model group relative to the controls [(13.93±3.35) mm2 vs. (2.79±0.94) mm2, P < 0.001 for diffusion area; (2.48±0.38) mm2 vs. (0.05±0.12) mm2, P < 0.001 for reflux area], with significant impairment of drainage in brain regions. The treatment group demonstrated significantly reduced tracer diffusion and reflux areas [(7.93±2.48) mm2 vs. (13.93±3.35) mm2, P < 0.001 for diffusion area; (0.50±0.30) mm2 vs. (2.48±0.38) mm2, P < 0.001 for reflux area]. Immunofluorescence staining revealed disrupted AQP4 polarity distribution and reduced AQP4 protein expression in the model group compared with the controls [(3 663.88±733.77) µm2 vs. (13 354.92±4 054.05) µm2, P < 0.001]. The treatment group exhibited restored AQP4 polarity distribution and elevated AQP4 protein expression [(11 104.68±3 200.04) µm2 vs. (3 663.88±733.77) µm2, P < 0.001]. CONCLUSION: UA intervention ameliorates behavioral performance in SZ mice, Thus alleviating hyperactivity and anxiety symptoms and restoring sensorimotor gating function. The underlying mechanism may involve the improvement of demyelination and ISF drainage dysregulation in SZ mice.


Asunto(s)
Enfermedades Desmielinizantes , Modelos Animales de Enfermedad , Líquido Extracelular , Ratones Endogámicos C57BL , Esquizofrenia , Triterpenos , Ácido Ursólico , Animales , Ratones , Triterpenos/uso terapéutico , Triterpenos/farmacología , Esquizofrenia/tratamiento farmacológico , Femenino , Enfermedades Desmielinizantes/tratamiento farmacológico , Líquido Extracelular/efectos de los fármacos , Líquido Extracelular/metabolismo , Maleato de Dizocilpina , Acuaporina 4/metabolismo
3.
Appl Opt ; 63(10): 2494-2502, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38568528

RESUMEN

Augmented reality (AR) near-eye displays have significantly progressed due to advances in nanostructure fabrication. However, for diffractive waveguide AR displays requiring exit pupil expansion, the angular uniformity of each exit pupil position still needs to improve. In this paper, an angular uniformity improvement method based on region geometry optimization is proposed. This optimization method essentially introduces the interaction number of the light with the grating as one of the variables to manipulate the energy distribution. This distribution is obtained by the rigorous coupled wave analysis (RCWA) method and ray tracing process and is further optimized by a multi-objective genetic algorithm. A model is built, and the feasibility of the proposed method is verified. The diffractive waveguide system has a 10m m×10m m exit pupil size at the eye relief of 25 mm and a field of view (FOV) of 21∘×12∘. After the optimization, the overall optical efficiency of the central field and the angular uniformity at the center exit pupil position increased from 0.9% and 66% to 3.1% and 80%, respectively.

4.
Foods ; 13(5)2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38472772

RESUMEN

Prunella vulgaris L. (PV) is a widely distributed plant species, known for its versatile applications in both traditional and contemporary medicine, as well as in functional food development. Despite its broad-spectrum antimicrobial utility, the specific mechanism of antibacterial action remains elusive. To fill this knowledge gap, the present study investigated the antibacterial properties of PV extracts against methicillin-resistant Staphylococcus aureus (MRSA) and assessed their mechanistic impact on bacterial cells and cellular functions. The aqueous extract of PV demonstrated greater anti-MRSA activity compared to the ethanolic and methanolic extracts. UPLC-ESI-MS/MS tentatively identified 28 phytochemical components in the aqueous extract of PV. Exposure to an aqueous extract at ½ MIC and MIC for 5 h resulted in a significant release of intracellular nucleic acid (up to 6-fold) and protein (up to 10-fold) into the extracellular environment. Additionally, this treatment caused a notable decline in the activity of several crucial enzymes, including a 41.51% reduction in alkaline phosphatase (AKP), a 45.71% decrease in adenosine triphosphatase (ATPase), and a 48.99% drop in superoxide dismutase (SOD). Furthermore, there was a decrease of 24.17% at ½ MIC and 27.17% at MIC in tricarboxylic acid (TCA) cycle activity and energy transfer. Collectively, these findings indicate that the anti-MRSA properties of PV may stem from its ability to disrupt membrane and cell wall integrity, interfere with enzymatic activity, and impede bacterial cell metabolism and the transmission of information and energy that is essential for bacterial growth, ultimately resulting in bacterial apoptosis. The diverse range of characteristics exhibited by PV positions it as a promising antimicrobial agent with broad applications for enhancing health and improving food safety and quality.

5.
Int Immunopharmacol ; 131: 111820, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38508092

RESUMEN

Exogenous hydrogen peroxide (H2O2) may generate excessive oxidative stress, inducing renal cell apoptosis related with kidney dysfunction. Geniposide (GP) belongs to the iridoid compound with anti-inflammatory, antioxidant and anti-apoptotic effects. This study aimed to observe the intervention effect of GP on H2O2-induced apoptosis in human kidney-2 (HK-2) cells and to explore its potential mechanism in relation to N6-methyladenosine (m6A) RNA methylation. Cell viability, apotosis rate and cell cycle were tested separately after different treatments. The mRNA and protein levels of m6A related enzymes and phosphoinositide 3-kinase (PI3K)/a serine/threonine-specific protein kinase 3 (AKT3)/forkhead boxo 1 (FOXO1) and superoxide dismutase 2 (SOD2) were detected by reverse transcription-quantitative real-time PCR (RT-qPCR) and Western blot. The whole m6A methyltransferase activity and the m6A content were measured by ELISA-like colorimetric methods. The changes of m6A methylation levels of PI3K/AKT3/FOXO1 and SOD2 were determined by methylated RNA immunoprecipitation (MeRIP)-qPCR. Multiple comparisons were performed by ANOVA with Turkey's post hoc test. Exposed to 400 µmol/L H2O2, cells were arrested in G1 phase and the apoptosis rate increased, which were significantly alleviated by GP. Compared with the H2O2 apoptosis group, both the whole m6A RNA methyltransferase activity and the m6A contents were increased due to GP intervention. Besides, the SOD2 protein was increased, while PI3K and FOXO1 decreased. The m6A methylation level of AKT3 was negatively correlated with its protein level. Taken together, GP affects the global m6A methylation microenvironment and regulates the expression of PI3K/AKT3/FOXO1 signaling pathway via m6A modification, alleviating cell cycle arrest and apoptosis caused by oxidative stress in HK-2 cells with a good application prospect.


Asunto(s)
Adenina , Fosfatidilinositol 3-Quinasa , Fosfatidilinositol 3-Quinasas , Humanos , Peróxido de Hidrógeno , Riñón , Iridoides/farmacología , Apoptosis , Estrés Oxidativo , ARN , Metiltransferasas , Proteína Forkhead Box O1 , Proteínas Proto-Oncogénicas c-akt
6.
Int J Biol Macromol ; 262(Pt 1): 130063, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38340925

RESUMEN

Waterborne polyurethanes (WPUs) often have limitations like inadequate weathering resistance and thermal stability. To overcome these shortcomings, lignin has been selected as a modifier for its abundant availability, renewability, and biocompatibility. This study synthesized a cationic WPU using isophorone diisocyanate and polyethylene glycol as raw materials. Hydrophilicity was attained through the inclusion of dihydroxyethyl dodecylamine as a chain extender, while the introduction of epoxy monomers and lignin served to modify the polyurethane. Furthermore, a dye dispersion for cotton fabric dyeing was prepared by combining the synthesized polyurethane, chitosan, and dyes. The cationic nature of the polyurethane played a crucial role in facilitating dye adhesion and uptake on the fabric surface, resulting in improved dyeing performance. The incorporation of epoxy side chains and chitosan cross-linking contributed to the excellent color fastness of the dyed fabrics. Moreover, the incorporation of lignin and chitosan endowed the fabric with antibacterial properties. Simultaneously, it provided effective UV protection, characterized by a high UV protection factor value for the fabrics. This lignin-modified WPU exhibits tremendous potential in applications such as textile coatings, adhesives, and color fixation agents. It effectively addresses the limitations of traditional WPUs and offers notable advantages, including a renewable source, cost-effectiveness, and biocompatibility.


Asunto(s)
Quitosano , Poliuretanos , Poliuretanos/química , Quitosano/química , Lignina , Textiles , Antibacterianos/química
7.
PLoS Pathog ; 20(2): e1012000, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38300973

RESUMEN

The early branching eukaryote Trypanosoma brucei divides uni-directionally along the longitudinal cell axis from the cell anterior toward the cell posterior, and the cleavage furrow ingresses along the cell division plane between the new and the old flagella of a dividing bi-flagellated cell. Regulation of cytokinesis in T. brucei involves actomyosin-independent machineries and trypanosome-specific signaling pathways, but the molecular mechanisms underlying cell division plane positioning remain poorly understood. Here we report a kinesin-13 family protein, KIN13-5, that functions downstream of FPRC in the cytokinesis regulatory pathway and determines cell division plane placement. KIN13-5 localizes to multiple cytoskeletal structures, interacts with FPRC, and depends on FPRC for localization to the site of cytokinesis initiation. Knockdown of KIN13-5 causes loss of microtubule bundling at both ends of the cell division plane, leading to mis-placement of the cleavage furrow and unequal cytokinesis, and at the posterior cell tip, causing the formation of a blunt posterior. In vitro biochemical assays demonstrate that KIN13-5 bundles microtubules, providing mechanistic insights into the role of KIN13-5 in cytokinesis and posterior morphogenesis. Altogether, KIN13-5 promotes microtubule bundle formation to ensure cleavage furrow placement and to maintain posterior cytoskeleton morphology in T. brucei.


Asunto(s)
Citocinesis , Trypanosoma brucei brucei , Citocinesis/fisiología , Trypanosoma brucei brucei/metabolismo , Cinesinas/genética , Cinesinas/metabolismo , Citoesqueleto/metabolismo , Microtúbulos/metabolismo , Morfogénesis , Proteínas Protozoarias/metabolismo
8.
Front Oncol ; 14: 1343533, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38410101

RESUMEN

Background: Uterine leiomyosarcoma(uLMS) is a rare malignant tumor with low clinical specificity and poor prognosis.There are many studies related to uLMS, however, there is still a lack of metrological analyses with generalization. This study provides a bibliometric study of uLMS. Methods and materials: We chose the Web of Science (WoS) as our main database due to its extensive interdisciplinary coverage. We specifically focused on the literature from the last 20 years to ensure relevance and practicality. By utilizing the WOS core dataset and leveraging the R package "bibliometric version 4.1.0" and Citespace, we performed a comprehensive bibliometric analysis. This allowed us to pinpoint research hotspots and create visual representations, resulting in the retrieval of 2489 pertinent articles. Results: This literature review covers 2489 articles on uterine leiomyosarcoma (uLMS) from the past 20 years. Key findings include an average annual publication rate of 8.75, with a 6.07% yearly growth rate and an average citation count of 17.22. Core+Zone 2 sources contributed 1079 articles and 207 reviews, displaying a 4.98% annual growth rate. The analysis identified top journals, influential authors, and core sources, such as the prevalence of publications from the United States and the dominance of GYNECOLOGIC ONCOLOGY and HENSLEY ML. Bradford's Law and Lotka's Law highlighted core sources and author productivity, respectively. Thematic mapping and factorial analysis revealed research clusters, including etiology, diagnosis, treatment advancements, and surgical approaches, with prominent themes such as gemcitabine and docetaxel. Overall, this comprehensive analysis provides insights into uLMS literature trends and influential factors. Conclusion: This thorough bibliometric analysis, in its whole, illuminates the field's guiding principles while also revealing the subtle patterns within the uLMS literature. The knowledge gained here contributes to the current discussion in uLMS and related scientific fields and provides a solid basis for future research paths.

9.
Ecotoxicol Environ Saf ; 271: 115928, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38215666

RESUMEN

Nephrotoxicity is a common adverse effect induced by various chemicals, necessitating the development of reliable toxicity screening models for nephrotoxicity assessment. In this study, we assessed a group of nephrotoxicity indicators derived from different toxicity pathways, including conventional endpoints and kidney tubular injury biomarkers such as clusterin (CLU), kidney injury molecule-I (KIM-1), osteopontin (OPN), and neutrophil gelatinase-associated lipocalin (NGAL), using HK-2 and induced pluripotent stem cells (iPSCs)-derived renal proximal tubular epithelial-like cells (PTLs). Among the biomarkers tested, OPN emerged as the most discerning and precise marker. The predictive potential of OPN was tested using a panel of 10 nephrotoxic and 5 non-nephrotoxic compounds. The results demonstrated that combining OPN with the half-maximal inhibitory concentration (IC50) enhanced the diagnostic accuracy in both cellular models. Additionally, PTLs cells showed superior predictive efficacy for nephrotoxicity compared to HK-2 cells in this investigation. The two cellular models were utilized to evaluate the nephrotoxicity of lanthanum. The findings indicated that lanthanum possesses nephrotoxic properties; however, the degree of nephrotoxicity was relatively low, consistent with the outcomes of in vivo experiments.


Asunto(s)
Lantano , Osteopontina , Humanos , Osteopontina/metabolismo , Lantano/toxicidad , Lantano/metabolismo , Riñón , Túbulos Renales/metabolismo , Biomarcadores/metabolismo
10.
J Biol Chem ; 299(11): 105340, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37838178

RESUMEN

The unicellular protozoan Trypanosoma brucei has a single flagellum that is involved in cell motility, cell morphogenesis, and cell division. Inheritance of the newly assembled flagellum during the cell cycle requires its correct positioning, which depends on the faithful duplication or segregation of multiple flagellum-associated cytoskeletal structures, including the basal body, the flagellum attachment zone, and the hook complex. Along the flagellum attachment zone sites a set of four microtubules termed the microtubule quartet (MtQ), whose molecular function remains enigmatic. We recently reported that the MtQ-localized protein NHL1 interacts with the microtubule-binding protein TbSpef1 and regulates flagellum inheritance by promoting basal body rotation and segregation. Here, we identified a TbSpef1- and NHL1-associated protein named SNAP1, which co-localizes with NHL1 and TbSpef1 at the proximal portion of the MtQ, depends on TbSpef1 for localization and is required for NHL1 localization to the MtQ. Knockdown of SNAP1 impairs the rotation and segregation of the basal body, the elongation of the flagellum attachment zone filament, and the positioning of the newly assembled flagellum, thereby causing mis-placement of the cell division plane, a halt in cleavage furrow ingression, and an inhibition of cytokinesis completion. Together, these findings uncover a coordinating role of SNAP1 with TbSpef1 and NHL1 in facilitating flagellum positioning and cell division plane placement for the completion of cytokinesis.


Asunto(s)
Flagelos , Microtúbulos , Proteínas Protozoarias , Trypanosoma brucei brucei , Cuerpos Basales/metabolismo , División Celular , Segregación Cromosómica , Flagelos/metabolismo , Microtúbulos/metabolismo , Proteínas Protozoarias/metabolismo , Trypanosoma brucei brucei/metabolismo
11.
Mol Oncol ; 17(12): 2694-2708, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37691307

RESUMEN

E3 SUMO-protein ligase CBX4 (CBX4), a key component of polycomb-repressive complexes 1 (PRC1), has been reported to regulate a variety of genes implicated in tumor growth, metastasis, and angiogenesis. However, its role in T-cell-mediated antitumor immunity remains elusive. To shed light on this issue, we generated mice with T-cell-specific deletion of Cbx4. Tumor growth was increased in the knockout mice. Additionally, their tumor-infiltrating lymphocytes exhibited impaired tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) production, with an elevated programmed cell death protein 1 (PD-1) level. In fact, dysregulated Pdcd1 expression was observed in all major subsets of peripheral T cells from the knockout mice, which was accompanied by a functional defect in response to T-cell receptor (TCR) stimulation. In support of a direct link between CBX4 and PD-1, Cbx4 overexpression resulted in the downregulation of Pdcd1 expression. Epigenetic analyses indicated that Cbx4 deficiency leads to diminished accumulation of inhibitory histone modifications at conserved region (CR)-C and CR-B sites of the Pdcd1 promoter, namely mono-ubiquitinated histone H2A at lysine 119 (H2AK119ub1) and trimethylated histone H3 at lysine 27 (H3K27me3). Moreover, inhibition of either the E3 ligase activity of polycomb-repressive complexes 1 (PRC1) or the methyltransferase activity of polycomb-repressive complexes 2 (PRC2) restores Pdcd1 expression in Cbx4-transfected cells. Cumulatively, this study reveals a novel function of CBX4 in the regulation of T-cell function and expands our understanding of the epigenetic control of Pdcd1 expression.


Asunto(s)
Neoplasias , Receptor de Muerte Celular Programada 1 , Animales , Ratones , Receptor de Muerte Celular Programada 1/genética , Lisina , Linfocitos T/metabolismo , Proteínas del Grupo Polycomb/genética , Proteínas del Grupo Polycomb/metabolismo , Ligasas/genética , Ligasas/metabolismo , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/metabolismo , Neoplasias/genética , Ratones Noqueados
12.
Food Chem Toxicol ; 180: 114005, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37640280

RESUMEN

Cadmium (Cd) causes bone loss, concerning inhibiting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Prunella vulgaris L. (PV) has the potential for promoting osteogenic differentiation, but its influence on Cd-induced bone loss is unclear. This study investigated the effect of PV aqueous extract (PVE) on Cd-induced bone loss and its underlying mechanisms. Eight-week-old female SD rats were randomly assigned into four groups and treated for 16 weeks: Control, Cd (50 mg/L of Cd chloride), Cd + PV Low (125 mg/kg bw of PVE), and Cd + PV High (250 mg/kg bw of PVE). PV ameliorated femoral bone loss in Cd-treated rats manifested as increases in bone mineral density, bone volume, trabecular thickness, number, and area, and decreases in trabecular separation. Compared with Cd group, PV-treatment groups had higher serum levels of bone formation markers (ALP, BGP). Additionally, in PV-treatment groups, expressions of bone formation markers (Osterix, Runx2) and molecules involved in osteogenic differentiation signal pathway BMP/Smad (BMP4, Smad1/5/9) in the tibia of rats and isolated rat primary BMSCs were upregulated. These results suggest that PV alleviates Cd-induced bone loss by promoting osteogenic differentiation, which is likely associated with BMP/Smad pathway.

13.
Front Plant Sci ; 14: 1127760, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37008510

RESUMEN

Cotton is an important fiber crop. The cotton fiber is an extremely long trichome that develops from the epidermis of an ovule. The trichome is a general and multi-function plant organ, and trichome birefringence-like (TBL) genes are related to trichome development. At the genome-wide scale, we identified TBLs in four cotton species, comprising two cultivated tetraploids (Gossypium hirsutum and G. barbadense) and two ancestral diploids (G. arboreum and G. raimondii). Phylogenetic analysis showed that the TBL genes clustered into six groups. We focused on GH_D02G1759 in group IV because it was located in a lint percentage-related quantitative trait locus. In addition, we used transcriptome profiling to characterize the role of TBLs in group IV in fiber development. The overexpression of GH_D02G1759 in Arabidopsis thaliana resulted in more trichomes on the stems, thereby confirming its function in fiber development. Moreover, the potential interaction network was constructed based on the co-expression network, and it was found that GH_D02G1759 may interact with several genes to regulate fiber development. These findings expand our knowledge of TBL family members and provide new insights for cotton molecular breeding.

14.
PLoS Pathog ; 19(3): e1011270, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36947554

RESUMEN

Microtubules constitute a vital part of the cytoskeleton in eukaryotes by mediating cell morphogenesis, cell motility, cell division, and intracellular transport. The cytoskeleton of the parasite Trypanosoma brucei contains an array of subpellicular microtubules with their plus-ends positioned toward the posterior cell tip, where extensive microtubule growth and cytoskeleton remodeling take place during early cell cycle stages. However, the control mechanism underlying microtubule dynamics at the posterior cell tip remains elusive. Here, we report that the S-phase cyclin-dependent kinase-cyclin complex CRK2-CYC13 in T. brucei regulates microtubule dynamics by phosphorylating ß-tubulin on multiple evolutionarily conserved serine and threonine residues to inhibit its incorporation into cytoskeletal microtubules and promote its degradation in the cytosol. Consequently, knockdown of CRK2 or CYC13 causes excessive microtubule extension and loss of microtubule convergence at the posterior cell tip, leading to cytoskeleton elongation and branching. These findings uncover a control mechanism for cytoskeletal microtubule dynamics by which CRK2 phosphorylates ß-tubulin and fine-tunes cellular ß-tubulin protein abundance to restrict excess microtubule extension for the maintenance of cytoskeleton architecture.


Asunto(s)
Trypanosoma brucei brucei , Tubulina (Proteína) , Tubulina (Proteína)/metabolismo , Trypanosoma brucei brucei/metabolismo , Microtúbulos/metabolismo , Citoesqueleto/metabolismo , Morfogénesis
15.
EClinicalMedicine ; 58: 101913, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36969336

RESUMEN

Background: Breast cancer is the leading cause of cancer-related deaths in women. However, accurate diagnosis of breast cancer using medical images heavily relies on the experience of radiologists. This study aimed to develop an artificial intelligence model that diagnosed single-mass breast lesions on contrast-enhanced mammography (CEM) for assisting the diagnostic workflow. Methods: A total of 1912 women with single-mass breast lesions on CEM images before biopsy or surgery were included from June 2017 to October 2022 at three centres in China. Samples were divided into training and validation sets, internal testing set, pooled external testing set, and prospective testing set. A fully automated pipeline system (FAPS) using RefineNet and the Xception + Pyramid pooling module (PPM) was developed to perform the segmentation and classification of breast lesions. The performances of six radiologists and adjustments in Breast Imaging Reporting and Data System (BI-RADS) category 4 under the FAPS-assisted strategy were explored in pooled external and prospective testing sets. The segmentation performance was assessed using the Dice similarity coefficient (DSC), and the classification was assessed using heatmaps, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. The radiologists' reading time was recorded for comparison with the FAPS. This trial is registered with China Clinical Trial Registration Centre (ChiCTR2200063444). Findings: The FAPS-based segmentation task achieved DSCs of 0.888 ± 0.101, 0.820 ± 0.148 and 0.837 ± 0.132 in the internal, pooled external and prospective testing sets, respectively. For the classification task, the FAPS achieved AUCs of 0.947 (95% confidence interval [CI]: 0.916-0.978), 0.940 (95% [CI]: 0.894-0.987) and 0.891 (95% [CI]: 0.816-0.945). It outperformed radiologists in terms of classification efficiency based on single lesions (6 s vs 3 min). Moreover, the FAPS-assisted strategy improved the performance of radiologists. BI-RADS category 4 in 12.4% and 13.3% of patients was adjusted in two testing sets with the assistance of FAPS, which may play an important guiding role in the selection of clinical management strategies. Interpretation: The FAPS based on CEM demonstrated the potential for the segmentation and classification of breast lesions, and had good generalisation ability and clinical applicability. Funding: This study was supported by the Taishan Scholar Foundation of Shandong Province of China (tsqn202211378), National Natural Science Foundation of China (82001775), Natural Science Foundation of Shandong Province of China (ZR2021MH120), and Special Fund for Breast Disease Research of Shandong Medical Association (YXH2021ZX055).

16.
Theor Appl Genet ; 136(3): 48, 2023 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-36912959

RESUMEN

KEY MESSAGE: The fiber length-related qFL-A12-5 identified in CSSLs introgressed from Gossypium barbadense into Gossypium hirsutum was fine-mapped to an 18.8 kb region on chromosome A12, leading to the identification of the GhTPR gene as a potential regulator of cotton fiber length. Fiber length is a key determinant of fiber quality in cotton, and it is a key target of artificial selection for breeding and domestication. Although many fiber length-related quantitative trait loci have been identified, there are few reports on their fine mapping or candidate gene validation, thus hampering efforts to understand the mechanistic basis of cotton fiber development. Our previous study identified the qFL-A12-5 associated with superior fiber quality on chromosome A12 in the chromosome segment substitution line (CSSL) MBI7747 (BC4F3:5). A single segment substitution line (CSSL-106) screened from BC6F2 was backcrossed to construct a larger segregation population with its recurrent parent CCRI45, thus enabling the fine mapping of 2852 BC7F2 individuals using denser simple sequence repeat markers to narrow the qFL-A12-5 to an 18.8 kb region of the genome, in which six annotated genes were identified in Gossypium hirsutum. Quantitative real-time PCR and comparative analyses led to the identification of GH_A12G2192 (GhTPR) encoding a tetratricopeptide repeat-like superfamily protein as a promising candidate gene for qFL-A12-5. A comparative analysis of the protein-coding regions of GhTPR among Hai1, MBI7747, and CCRI45 revealed two non-synonymous mutations. The overexpression of GhTPR resulted in longer roots in Arabidopsis, suggesting that GhTPR may regulate cotton fiber development. These results provide a foundation for future efforts to improve cotton fiber length.


Asunto(s)
Gossypium , Sitios de Carácter Cuantitativo , Humanos , Gossypium/genética , Mapeo Cromosómico/métodos , Fenotipo , Fitomejoramiento , Fibra de Algodón , Estudios de Asociación Genética
17.
Food Chem Toxicol ; 172: 113601, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36610472

RESUMEN

Cadmium accumulates in the kidney and causes inflammation. The NLRP3 inflammasome has been linked to the pathogenesis of inflammation. Hyperoside (HYP) possesses potent nephroprotective properties against of kidney injury. This study aimed to research the effects and related mechanism of HYP on Cd-induced kidney damage. Wide-type and NLRP3-/- mice were used to determine the role of NLRP3 inflammasome in Cd-induced renal dysfunction. Female C57BL/6 were treated with Cd (50 m,g/L) and HYP (25, 50 mg/kg) for 12 weeks. In vitro experiments, the human renal proximal-tubule epithelial cells (RPTEC/TERT1) were pretreated with HYP (50-200 µM) before exposure to Cd. NLRP3 deficiency attenuated Cd-induced NLRP3 activation, inflammation and kidney injury in mice. HYP treatment significantly alleviated Cd-induced kidney injury by decreasing indexes of kidney function, reducing pro-inflammatory cytokines release, decreasing ROS production and suppressing NLRP3 inflammasome activation. Moreover, treatment with siRNA targeting NLRP3 blocked the anti-inflammatory protective effect of HYP in Cd-treated cells. Additionally, HYP markedly inhibited Cd-induced MAPK/NF-κB pathway stimulation in vitro and in vivo. The findings indicated HYP conferred protection against Cd-induced kidney inflammation via suppression of NLRP3 inflammasome mediated by ROS/MAPK/NF-κB signaling. Our results thus support the notion of developing HYP as promising therapeutic candidate for Cd-induced kidney injury.


Asunto(s)
Inflamasomas , FN-kappa B , Humanos , Femenino , Ratones , Animales , FN-kappa B/metabolismo , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Cadmio/toxicidad , Cadmio/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ratones Endogámicos C57BL , Transducción de Señal , Riñón , Inflamación/metabolismo
19.
Opt Express ; 30(12): 21478-21490, 2022 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-36224866

RESUMEN

A multi-directional backlight autostereoscopic display system with high resolution, low crosstalk, and motion parallax is developed in this paper. The proposed multi-directional backlight system is based on the Bragg mismatched reconstruction of volume holographic optical element (VHOE), and includes a set of light sources which are uniformly arrayed along one direction. Each light source produces its corresponding directional lighting to follow the human eye position detected by an eye tracker. Two scenarios are presented to build the multi-directional backlight system. The prism-type backlight system which guides the incident beam with a prism is relatively simple and easy to implement. The waveguide-type one which employs a transflective film to expand the incident light beam within the waveguide and modulate the intensity of the incident beam, is relatively thin and is applicable to large-area display. Two prototypes are built and the effectiveness of the proposed autostereoscopic display system is verified by the experimental results.

20.
Open Biol ; 12(10): 220197, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36196534

RESUMEN

Cytokinesis in eukaryotes is regulated by a Polo-like kinase-mediated and Aurora B kinase-mediated signalling pathway that promotes the assembly of the actomyosin contractile ring, a cytokinesis machinery conserved across evolution from yeast to humans. Trypanosoma brucei, an early divergent parasitic protozoan, employs an actomyosin-independent mechanism for its unusual cytokinesis that is controlled by a regulatory pathway comprising the Polo-like kinase TbPLK, the Aurora B kinase TbAUK1 and multiple trypanosomatid-specific regulators. However, whether any of these trypanosomatid-specific regulators function as substrates of TbPLK and/or TbAUK1 and how they cooperate with TbPLK and TbAUK1 to promote cytokinesis remain unknown. Here, we demonstrate that TbPLK and TbAUK1 phosphorylate the cytokinesis regulators CIF1 and CIF2 on multiple sites within their intrinsically disordered regions. We further show that TbPLK localization depends on its interaction with CIF1 from S/G2 phases, that TbPLK maintains CIF1 and CIF2 localization from G2 phase until early mitosis, and that TbAUK1 maintains CIF1 and CIF2 localization from late mitosis. Finally, we demonstrate that the cytokinesis regulators CIF4 and FPRC are not substrates of TbPLK and TbAUK1, and that they function upstream of TbPLK and TbAUK1 in the cytokinesis regulatory pathway. Together, these results provide insights into the functional interplay and the order of actions between the two protein kinases and the trypanosomatid-specific cytokinesis regulators in T. brucei.


Asunto(s)
Trypanosoma brucei brucei , Actomiosina/metabolismo , Aurora Quinasa B/genética , Aurora Quinasa B/metabolismo , Citocinesis/fisiología , Humanos , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Trypanosoma brucei brucei/metabolismo
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