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1.
J Genet Genomics ; 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38642801

RESUMEN

Hetero-tetrameric soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) complexes are critical for vesicle-target membrane fusion within the endomembrane system of eukaryotic cells. SNARE assembly involves four different SNARE motifs, Qa, Qb, Qc, and R, provided by three or four SNARE proteins. YKT6 is an atypical R-SNARE that lacks a transmembrane domain and is involved in multiple vesicle-target membrane fusions. Although YKT6 is evolutionarily conserved and essential, its function and regulation in different phyla seem distinct. Arabidopsis YKT61, the yeast and metazoan YKT6 homologue, is essential for gametophytic development, plays a critical role in sporophytic cells, and mediates multiple vesicle-target membrane fusion. However, its molecular regulation is unclear. We report here that YKT61 is S-acylated. Abolishing its S-acylation by a C195S mutation dissociates YKT61 from endomembrane structures and causes its functional loss. Although interacting with various SNARE proteins, YKT61 functions not as a canonical R-SNARE but coordinates with other R-SNAREs to participate in the formation of SNARE complexes. Phylum-specific molecular regulation of YKT6 may be evolved to allow more efficient SNARE assembly in different eukaryotic cells.

2.
Plant Sci ; 344: 112090, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38636812

RESUMEN

Vacuoles are the largest membrane-bound organelles in plant cells, critical for development and environmental responses. Vacuolar dynamics indicate reversible changes of vacuoles in morphology, size, or numbers. In this review, we summarize current understandings of vacuolar dynamics in different types of plant cells, biological processes associated with vacuolar dynamics, and regulators controlling vacuolar dynamics. Specifically, we point out the possibility that vacuolar dynamics play key roles in cell division and differentiation, which are controlled by the nucleus. Finally, we propose three routes through which vacuolar dynamics actively participate in nucleus-controlled cellular activities.


Asunto(s)
Diferenciación Celular , División Celular , Células Vegetales , Vacuolas , Vacuolas/metabolismo , Vacuolas/fisiología , División Celular/fisiología , Células Vegetales/fisiología , Núcleo Celular/fisiología , Núcleo Celular/metabolismo
3.
bioRxiv ; 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38464098

RESUMEN

Purpose: Metabolic defects in retinal pigment epithelium (RPE) are underlying many retinal degenerative diseases. This study aims to identify the nutrient requirements of healthy and diseased human RPE cells. Methods: We profiled the utilization of 183 nutrients in human RPE cells: 1) differentiated and dedifferentiated fetal RPE (fRPE), 2) induced pluripotent stem cell derived-RPE (iPSC RPE), 3) Sorsby fundus dystrophy (SFD) patient-derived iPSC RPE and its CRISPR-corrected isogenic SFD (cSFD) iPSC RPE, and 5) ARPE-19 cell lines cultured under different conditions. Results: Differentiated fRPE cells and healthy iPSC RPE cells can utilize 51 and 48 nutrients respectively, including sugars, intermediates from glycolysis and tricarboxylic acid (TCA) cycle, fatty acids, ketone bodies, amino acids, and dipeptides. However, when fRPE cells lose epithelial phenotype through dedifferentiated, they can only utilize 17 nutrients, primarily sugar and glutamine-related amino acids. SFD RPE cells can utilize 37 nutrients; however, Compared to cSFD RPE and healthy iPSC RPE, they are unable to utilize lactate, some TCA cycle intermediates, and short-chain fatty acids. Nonetheless, they show increased utilization of branch-chain amino acids (BCAAs) and BCAA-containing dipeptides. The dedifferentiated ARPE-19 cells in traditional culture media cannot utilize lactate and ketone bodies. In contrast, nicotinamide supplementation promotes differentiation into epithelial phenotype, restoring the ability to use these nutrients. Conclusions: Epithelial phenotype confers metabolic flexibility to the RPE for utilizing various nutrients. SFD RPE cells have reduced metabolic flexibility, relying on the oxidation of BCAAs. Our findings highlight the importance of nutrient availability and utilization in RPE differentiation and diseases.

4.
J Biomol Struct Dyn ; : 1-17, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38379386

RESUMEN

Diabetic nephropathy (DN) is one of the most feared complications of diabetes and key cause of end-stage renal disease (ESRD). Berberis integerrima has been widely used to treat diabetic complications, but exact molecular mechanism is yet to be discovered. Data on active ingredients of B. integerrima and target genes of both diabetic nephropathy and B.integerrima were obtained from public databases. Common results between B. integerrima and DN targets were used to create protein-protein interaction (PPI) network using STRING database and exported to Cytoscape software for the selection of hub genes based on degree of connectivity. Future, PPI network between constituents and overlapping targets was created using Cytoscape to investigate the network pharmacological effects of B. integerrima on DN. KEGG pathway analysis of core genes exposed their involvement in excess glucose-activated signaling pathway. Then, expression of core genes was validated through machine learning classifiers. Finally, PyRx and AMBER18 software was used for molecular docking and simulation. We found that Armepavine, Berberine, Glaucine, Magnoflorine, Reticuline, Quercetin inhibits the growth of diabetic nephropathy by affecting ICAM1, PRKCB, IKBKB, KDR, ALOX5, VCAM1, SYK, TBXA2R, LCK, and F3 genes. Machine learning revealed SYK and PRKCB as potential genes that could use as diagnostic biomarkers against DN. Furthermore, docking and simulation analysis showed the binding affinity and stability of the active compound with target genes. Our study revealed that B. integerrima has preventive effect on DN by acting on glucose-activated signaling pathways. However, experimental studies are needed to reveal biosafety profiles of B. integerrima in DN.Communicated by Ramaswamy H. Sarma.

5.
Proc Natl Acad Sci U S A ; 121(7): e2322375121, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38315835

RESUMEN

Protein S-acyl transferases (PATs) catalyze S-acylation, a reversible post-translational modification critical for membrane association, trafficking, and stability of substrate proteins. Many plant proteins are potentially S-acylated but few have corresponding PATs identified. By using genomic editing, confocal imaging, pharmacological, genetic, and biochemical assays, we demonstrate that three Arabidopsis class C PATs positively regulate BR signaling through S-acylation of BRASSINOSTEROID-SIGNALING KINASE1 (BSK1). PAT19, PAT20, and PAT22 associate with the plasma membrane (PM) and the trans-Golgi network/early endosome (TGN/EE). Functional loss of all three genes results in a plethora of defects, indicative of reduced BR signaling and rescued by enhanced BR signaling. PAT19, PAT20, and PAT22 interact with BSK1 and are critical for the S-acylation of BSK1, and for BR signaling. The PM abundance of BSK1 was reduced by functional loss of PAT19, PAT20, and PAT22 whereas abolished by its S-acylation-deficient point mutations, suggesting a key role of S-acylation in its PM targeting. Finally, an active BR analog induces vacuolar trafficking and degradation of PAT19, PAT20, or PAT22, suggesting that the S-acylation of BSK1 by the three PATs serves as a negative feedback module in BR signaling.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas Serina-Treonina Quinasas , Acilación , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Brasinoesteroides/metabolismo , Regulación de la Expresión Génica de las Plantas , Transducción de Señal , Transferasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo
6.
Mol Biol Rep ; 51(1): 113, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38227102

RESUMEN

BACKGROUND: Essential tremor (ET) is a neurological disease characterized by action tremor in upper arms. Although its high heritability and prevalence worldwide, its etiology and association with other diseases are still unknown. METHOD: We investigated 10 common spinocerebellar ataxias (SCAs), including SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, SCA17, SCA36, dentatorubral-pallidoluysian atrophy (DRPLA) in 92 early-onset familial ET pedigrees in China collected from 2016 to 2022. RESULT: We found one SCA12 proband carried 51 CAG repeats within PPP2R2B gene and one SCA3 proband with intermediate CAG repeats (55) with ATXN3 gene. The other 90 ET probands all had normal repeat expansions. CONCLUSION: Tremor can be the initial phenotype of certain SCA. For early-onset, familial ET patients, careful physical examinations are needed before genetic SCA screening.


Asunto(s)
Temblor Esencial , Ataxias Espinocerebelosas , Humanos , Temblor Esencial/epidemiología , Temblor Esencial/genética , China/epidemiología , Ataxias Espinocerebelosas/epidemiología , Ataxias Espinocerebelosas/genética , Nucleótidos
7.
J Hum Nutr Diet ; 37(1): 354-364, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37897115

RESUMEN

BACKGROUND: To explore the association between the diet inflammatory index (DII) and infertility. METHODS: Multivariable logistic regression was performed to investigate the relationship between infertility and DII, and restricted cubic spline (RCS) was utilised to test for nonlinear relationships in this cross-sectional study. Data of this study were collected from the 2013 to 2020 National Health and Nutrition Examination Survey (NHANES) database. Considering women's child-bearing age, we enrolled a total of 2066 women aged 20-45 years in this study. RESULTS: After all covariates were adjusted, a positive association was found between DII score and odds of infertility by multivariable logistic regression (odds ratio [OR] = 1.19, 95% confidence interval [CI] 1.03, 1.38; p = 0.027). Compared with participants with DII scores in the lowest quartile, those with DII scores in the highest quartile had significantly higher odds of infertility (OR = 2.42, 95% CI 1.09, 5.34; p = 0.034). The RCSs model suggested a linear relationship between DII and infertility (p for nonlinear = 0.1827). CONCLUSIONS: A positive association between a pro-inflammatory diet and self-reported infertility was detected. Our study extends the application of the DII scoring system to infertility prevention.


Asunto(s)
Infertilidad Femenina , Inflamación , Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Encuestas Nutricionales , Inflamación/epidemiología , Estudios Transversales , Autoinforme , Infertilidad Femenina/epidemiología , Infertilidad Femenina/etiología , Dieta/efectos adversos
8.
Nanomaterials (Basel) ; 13(11)2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37299643

RESUMEN

In this paper, the effect of atomic layer deposition (ALD)-derived Al2O3 passivation layers and annealing temperatures on the interfacial chemistry and transport properties of sputtering-deposited Er2O3 high-k gate dielectrics on Si substrate has been investigated. X-ray photoelectron spectroscopy (XPS) analyses have showed that the ALD-derived Al2O3 passivation layer remarkably prevents the formation of the low-k hydroxides generated by moisture absorption of the gate oxide and greatly optimizes the gate dielectric properties. Electrical performance measurements of metal oxide semiconductor (MOS) capacitors with different gate stack order have revealed that the lowest leakage current density of 4.57 × 10-9 A/cm2 and the smallest interfacial density of states (Dit) of 2.38 × 1012 cm-2 eV-1 have been achieved in the Al2O3/Er2O3/Si MOS capacitor, which can be attributed to the optimized interface chemistry. Further electrical measurements of annealed Al2O3/Er2O3/Si gate stacks at 450 °C have demonstrated superior dielectric properties with a leakage current density of 1.38 × 10-9 A/cm2. At the same, the leakage current conduction mechanism of MOS devices under various stack structures is systematically investigated.

9.
Mar Pollut Bull ; 190: 114871, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37023546

RESUMEN

As a broad-spectrum nicotinoid insecticide, imidacloprid (IMI) has been frequently recorded in seawater environments. Water quality criteria (WQC) is the maximum concentration of chemicals, which will not pose harmful effects on aquatic species in the studied water body. Nevertheless, the WQC is not available for IMI in China, which hinders the risk assessment of this emerging pollutant. This study, therefore, aims to derive the WQC for IMI through the toxicity percentile rank (TPR) and species sensitivity distribution (SSD) methodology, and to assess its ecological risk in aquatic environments. Results showed that the recommended short-term water quality criterion (SWQC) and long-term criterion (LWQC) in seawater were derived as 0.8 µg/L and 0.056 µg/L, respectively. The ecological risk of IMI in seawater shows a wide range with hazard quotient (HQ) values of up to 11.4. The environmental monitoring, risk management and pollution control for IMI, therefore, warrant further study.


Asunto(s)
Insecticidas , Contaminantes Químicos del Agua , Organismos Acuáticos , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Calidad del Agua , Medición de Riesgo/métodos , Neonicotinoides/farmacología , China
10.
J Mol Neurosci ; 73(4-5): 205-213, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36929462

RESUMEN

Genetic factors play a major role in essential tremor (ET) pathogenesis. This study aimed to assess variant burden in ET-associated genes in a relatively large Chinese population cohort. We genotyped 27 single nucleotide polymorphisms (SNPs) previously reported to be associated with ET by multiplex PCR amplicon sequencing assay in 488 familial and sporadic ET patients and 514 healthy controls (HCs). Then, we performed allelic and genotypic association test by Pearson chi-square test or Fisher's exact test. A total of 1002 samples were included in our analysis, consisting of 488 ET patients and 514 sex and age-matched HCs. For rs10937625, the C allele was linked to increased risk of ET (P = 0.019, OR = 1.503, 95% CI = 1.172-1.928). The carriers of the C/C homozygote and C/T heterozygote showed a significantly higher risk of ET, compared with the T/T homozygote under the dominant model (P = 0.019, OR = 1.628, 95% CI = 1.221-2.170). There were no statistically significant differences in the frequency of other SNPs between ET patients and healthy controls. Rs10937625 (STK32B) may increase the risk of ET in eastern Chinese population.


Asunto(s)
Temblor Esencial , Predisposición Genética a la Enfermedad , Humanos , Estudios de Casos y Controles , China/epidemiología , Pueblos del Este de Asia , Temblor Esencial/genética , Frecuencia de los Genes , Genotipo , Polimorfismo de Nucleótido Simple , Proteínas Serina-Treonina Quinasas/genética
11.
Sci Rep ; 13(1): 3418, 2023 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-36854769

RESUMEN

Membranous nephropathy is the main cause of nephrotic syndrome, which has an insidious onset and may progress to end-stage renal disease with a high mortality rate, such as renal failure and uremia. At present, the diagnosis of membranous nephropathy mainly relies on the clinical manifestations of patients and pathological examination of kidney biopsy, which are expensive, time-consuming, and have certain chance and other disadvantages. Therefore, there is an urgent need to find a rapid, accurate and non-invasive diagnostic technique for the diagnosis of membranous nephropathy. In this study, Raman spectra of serum and urine were combined with deep learning methods to diagnose membranous nephropathy. After baseline correction and smoothing of the data, Gaussian white noise of different decibels was added to the training set for data amplification, and the amplified data were imported into ResNet, AlexNet and GoogleNet models to obtain the evaluation results of the models for membranous nephropathy. The experimental results showed that the three deep learning models achieved an accuracy of 1 for the classification of serum data of patients with membranous nephropathy and control group, and the discrimination of urine data was above 0.85, among which AlexNet was the best classification model for both samples. The above experimental results illustrate the great potential of serum- and urine-based Raman spectroscopy combined with deep learning methods for rapid and accurate identification of patients with membranous nephropathy.


Asunto(s)
Líquidos Corporales , Aprendizaje Profundo , Glomerulonefritis Membranosa , Fallo Renal Crónico , Insuficiencia Renal , Humanos , Glomerulonefritis Membranosa/diagnóstico , Espectrometría Raman
12.
J Neurol ; 270(4): 2106-2116, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36609498

RESUMEN

OBJECTIVE: Essential tremor (ET) is the second most common movement disorder; however, the pathophysiological mechanism of ET is unclear. We aimed to investigate the microstructural degeneration of gray matter (GM) and white matter (WM) and their correlations with cognition and tremor in patients with ET. METHODS: The participants were 63 patients with ET and 63 matched healthy controls (HCs) who underwent 3D-T1 weighted and diffusion kurtosis images (DKI). Microstructural degeneration was measured using high-level diffusion parameters derived from DKI. A voxel-wise analysis of the means of the GM-based spatial statistics and tract-based spatial statistics were conducted to assess differences in diffusion parameters between the ET and HC groups. The volume differences between the two groups were also assessed, and tremor severity and multi-domain cognitive performance were evaluated. Finally, the relationship between microstructural degeneration and clinical characteristics were assessed. RESULTS: The ET group had significantly lower mean kurtosis of the temporal, parietal, and occipital lobes and the cerebellum and lower radial kurtosis in several tracts. These microstructural changes in GM and WM were correlated with tremor and cognitive scores. However, no significant difference in volume was found between the groups. CONCLUSION: Our findings suggest that ET entails extensive GM and WM microstructural alterations, which support the neurodegenerative hypothesis of ET. Our study contributes to a better understanding of the mechanisms underlying tremor and cognitive impairment in ET.


Asunto(s)
Temblor Esencial , Sustancia Blanca , Humanos , Temblor Esencial/diagnóstico por imagen , Temblor , Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Sustancia Gris/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen
13.
PLoS One ; 18(1): e0280320, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36649274

RESUMEN

PURPOSE: To predict pathological complete response (pCR) after neoadjuvant chemotherapy using extreme gradient boosting (XGBoost) with MRI and non-imaging data at multiple treatment timepoints. MATERIAL AND METHODS: This retrospective study included breast cancer patients (n = 117) who underwent neoadjuvant chemotherapy. Data types used included tumor ADC values, diffusion-weighted and dynamic-contrast-enhanced MRI at three treatment timepoints, and patient demographics and tumor data. GLCM textural analysis was performed on MRI data. An extreme gradient boosting machine learning algorithm was used to predict pCR. Prediction performance was evaluated using the area under the curve (AUC) of the receiver operating curve along with precision and recall. RESULTS: Prediction using texture features of DWI and DCE images at multiple treatment time points (AUC = 0.871; 95% CI: (0.768, 0.974; p<0.001) and (AUC = 0.903 95% CI: 0.854, 0.952; p<0.001) respectively), outperformed that using mean tumor ADC (AUC = 0.850 (95% CI: 0.764, 0.936; p<0.001)). The AUC using all MRI data was 0.933 (95% CI: 0.836, 1.03; p<0.001). The AUC using non-MRI data was 0.919 (95% CI: 0.848, 0.99; p<0.001). The highest AUC of 0.951 (95% CI: 0.909, 0.993; p<0.001) was achieved with all MRI and all non-MRI data at all time points as inputs. CONCLUSION: Using XGBoost on extracted GLCM features and non-imaging data accurately predicts pCR. This early prediction of response can minimize exposure to toxic chemotherapy, allowing regimen modification mid-treatment and ultimately achieving better outcomes.


Asunto(s)
Neoplasias de la Mama , Imágenes de Resonancia Magnética Multiparamétrica , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Imagen de Difusión por Resonancia Magnética/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Imagen por Resonancia Magnética/métodos , Terapia Neoadyuvante/métodos , Aprendizaje Automático
14.
Parkinsonism Relat Disord ; 107: 105254, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36584484

RESUMEN

INTRODUCTION: Growing evidence has demonstrated dysfunction of the glymphatic system in α-synucleinopathy and related diseases. In this study, we aimed to use diffusion tensor image analysis along the perivascular space (DTI-ALPS) and MRI-visible enlarged perivascular spaces (EPVS) to evaluate glymphatic system function quantitatively and qualitatively and its relationship to clinical scores of disease severity in Parkinson's disease (PD) and essential tremor (ET). METHODS: Overall, 124 patients with PD, 74 with ET, and 106 healthy controls (HC) were enrolled. Two trained neurologists performed quantitative calculations of ALPS on DTI and visual ratings of EPVS on T2-weighted images in the centrum semiovale (CSO), basal ganglia (BG), midbrain, and cerebellum. RESULTS: The ALPS index was lower in patients with PD than in patients with ET (p < 0.001) and HC (p < 0.001). Similarly, patients with PD showed a more severe EPVS burden in the CSO, BG, and midbrain compared to ET and HC. Moreover, the ALPS index was negatively correlated with disease severity in the PD subgroups; however, it did not differ within the ET subgroup. No differences in ALPS or EPVS were observed between the ET and HC groups. CONCLUSION: In conclusion, DTI-ALPS and EPVS both provide neuroimaging evidence of glymphatic system dysfunction in PD, which further supports that PD is an α-synucleinopathy disease, while ET is a cerebellar dysfunction-related disease.


Asunto(s)
Temblor Esencial , Sistema Glinfático , Enfermedad de Parkinson , Sinucleinopatías , Humanos , Enfermedad de Parkinson/diagnóstico por imagen , Sistema Glinfático/diagnóstico por imagen , Temblor Esencial/diagnóstico por imagen , Neuroimagen , Imagen por Resonancia Magnética
16.
J Neurol ; 270(2): 780-787, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36194299

RESUMEN

BACKGROUND: The pathophysiology of essential tremor (ET) is not fully understood, and studies suggest pathological changes mainly occur in the cerebellum and locus coeruleus (LC). METHODS: Fifty-three ET patients, including 30 patients with head tremor (h-ET), 23 patients without head tremor (nh-ET), 71 age and education matched healthy controls (HCs) were enrolled. All participants underwent Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and T1 scans on a 3-Tesla MR system. Next, we assessed the relationship between the contrast-to-noise ratio of LC (CNRLC) and the score of The Essential Tremor Rating Assessment Scale (TETRAS) and cerebellum gray matter (GM) volume. RESULTS: Significant difference of CNRLC was found between ET and HC groups. The CNRLC of ET groups is lower than the HC group (p = 0.031). Subgroup analysis showed that the CNRLC in nh-ET was significantly lower than HCs (p = 0.016). Compared to HCs, h-ETs showed marked atrophy in the cerebellum: the vermis IV-V and lobule VI (GRF corrected, p < 0.05). A significant negative correlation was found between CNRLC and the vermis lobule IV-V in h-ETs (r = - 0.651, p < 0.001). No significant correlation was found between CNRLC and TETRAS scores. CONCLUSION: The LC and the cerebellum might both involve in the pathophysiology of ET. LC evaluation using NM-MRI might be an effective tool for us to explore the pathophysiology of ET further.


Asunto(s)
Temblor Esencial , Sustancia Gris , Humanos , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Temblor Esencial/diagnóstico por imagen , Temblor Esencial/patología , Temblor/patología , Locus Coeruleus/diagnóstico por imagen , Locus Coeruleus/patología , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Imagen por Resonancia Magnética/métodos
17.
Ann Med Surg (Lond) ; 84: 104900, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36536730

RESUMEN

Background: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is an important prognostic indicator in breast cancer. Internal mammary lymph node involvement is not currently included in pCR determination, as sampling at the time of surgery is not routinely performed. Methods: Pre and post neoadjuvant chemotherapy MRI or PET/CT imaging response of the internal mammary lymph node chain was utilized as a surrogate to pCR and imaging data was correlated with patient outcomes. Results: Internal mammary lymph node response to NAC was associated with disease free survival over the course of this study, regardless of whether axillary nodal pCR was achieved. Conclusion: Internal mammary lymph nodal response to NAC is an important prognostic indicator. Potential use of internal mammary lymph node resolution as an imaging data input for AI models that predict pCR post-NAC may improve accuracy and other metrics in pCR prediction.

18.
BMC Pregnancy Childbirth ; 22(1): 838, 2022 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-36376855

RESUMEN

BACKGROUND: The impact of smooth endoplasmic reticulum aggregates (SERa) on assisted reproductive technology (ART) outcomes was still controversial. Our objective is to investigate the impact of the presence of SERa on intracytoplasmic sperm injection (ICSI) outcomes. METHODS: This was a retrospective cohort study. A total of 1,090 fresh ICSI cycles from 944 patients between January 2016 and June 2020 were included. Outcomes from clinical, embryological and neonatal aspects were compared between SERa + and SERa- cycles as well as between SERa + and SERa- oocytes. RESULTS: The total gonadotropin (Gn) dose, number of oocytes retrieved, serum estradiol concentration and number of the available embryo were significantly higher in SERa + cycles than in SERa- cycles (P < 0.05). Comparable two pronuclei (2PN) fertilization rate and poly-pronucleus zygote rate were shown in SERa + and SERa- cycles (P > 0.05), but which were higher in SERa + oocytes than in SERa- oocytes (P < 0.05). No statistical difference in blastocyst formation rate was found in SERa + and SERa- cycles as well as in SERa + and SERa- oocytes (P > 0.05). Good-quality embryo rate was statistically higher in SERa- cycles than in SERa + cycles (P < 0.05), but the difference was comparable between SERa + and SERa- oocytes (P > 0.05). No statistical difference in clinical pregnancy rate, spontaneous abortion rate, live birth rate and premature delivery rate were found in SERa + and SERa- cycles as well as in SERa + and SERa- oocytes (P > 0.05). The implantation rate was comparable in SERa + and SERa- cycles (P > 0.05), but it is higher in the group of only SERa- embryo transfer when compared with the group of mixed SERa + and SERa- embryo transfer (P < 0.05). 159 newborns in SERa + cycles and 140 newborns in SERa- cycles were followed up. Comparable newborn malformation rate was observed between SERa + and SERa- cycles and oocytes (P > 0.05). Logistic regression analysis revealed number of oocytes and total dose of Gn were risk factors for SERa occurrence (aOR = 1.05 and 1.55, P < 0.001). CONCLUSION: Oocyte's SERa is correlated with a number of oocytes retrieved and higher Gn dose, but it does not affect pregnancy outcomes and increase newborn malformation rate.


Asunto(s)
Fertilización In Vitro , Semen , Embarazo , Femenino , Masculino , Humanos , Estudios Retrospectivos , Estudios de Cohortes , Índice de Embarazo , Oocitos , Resultado del Embarazo , Gonadotropinas , Retículo Endoplásmico Liso
19.
Cell Rep ; 41(7): 111640, 2022 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-36384105

RESUMEN

Precise organ size control is fundamental for all metazoans, but how organ size is controlled in a three-dimensional (3D) way remains largely unexplored at the molecular level. Here, we screen and identify Drosophila Ptp61F as a pivotal regulator of organ size that integrates the Hippo pathway, TOR pathway, and actomyosin machinery. Pathologically, Ptp61F loss synergizes with RasV12 to induce tumorigenesis. Physiologically, Ptp61F depletion increases body size and drives neoplastic intestinal tumor formation and stem cell proliferation. Ptp61F also regulates cell contractility and myosin activation and controls 3D cell shape by reducing cell height and horizontal cell size. Mechanistically, Ptp61F forms a complex with Expanded (Ex) and increases endosomal localization of Ex and Yki. Furthermore, we demonstrate that PTPN2, the conserved human ortholog of Ptp61F, can functionally substitute for Ptp61F in Drosophila. Our work defines Ptp61F as an essential determinant that controls 3D organ size under both physiological and pathological conditions.


Asunto(s)
Actomiosina , Proteínas de Drosophila , Animales , Humanos , Proteínas de Drosophila/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas Serina-Treonina Quinasas/genética , Tamaño de los Órganos , Transactivadores/metabolismo , Proteínas Nucleares/metabolismo , Drosophila/metabolismo , Proteínas Tirosina Fosfatasas no Receptoras
20.
Appl Immunohistochem Mol Morphol ; 30(9): 614-622, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-36048167

RESUMEN

INTRODUCTION: Neoadjuvant endocrine therapy (NET) can be used to treat estrogen receptor positive (ER+) invasive breast cancer (IBC). Tumors with Ki67>10% after 2 to 4 weeks of NET are considered resistant to endocrine therapy. Enhancer of Zeste Homolog 2 (EZH2) is a targetable oncoprotein and overexpression in ER+ IBC has been linked to resistance to endocrine therapy. We examined whether EZH2 expression levels in ER+ IBC could be used to predict response to NET. MATERIALS AND METHODS: We retrospectively identified 46 patients with localized ER+ HER2/neu negative IBC treated with a minimum of 4 weeks of NET. We quantified EZH2 nuclear expression in pretherapy core biopsies using a score that included intensity and percent of cells staining. Ki67 was evaluated in both pretherapy core biopsies and posttherapy tumor resections and scored according to the guidelines of the International Ki67 Working Groups, with a global weighted score. Ki67≤10% after NET was considered endocrine responsive. Logistic regression analysis was performed to determine the association between EZH2 expression and response to NET. RESULTS: We found significant associations of tumor grade ( P =0.011), pretherapy Ki67 ( P =0.003), and EZH2 ( P <0.001), with response to NET. On logistic regression adjusted for tumor grade and pretherapy Ki67, increased EZH2 scores were associated with decreased odds of endocrine responsiveness, defined as posttreatment Ki67≤10% (odds ratio=0.976, 95% CI, 0.956 to 0.997; P =0.026). In addition, with EZH2 score in the model, associations of tumor grade and pretreatment Ki67 with posttreatment Ki67≤10% response to NET became not significant. CONCLUSIONS: Our results suggest that EZH2 might be a useful biomarker to predict response to NET.


Asunto(s)
Neoplasias de la Mama , Proteína Potenciadora del Homólogo Zeste 2 , Terapia Neoadyuvante , Neoplasias de la Mama/patología , Proteína Potenciadora del Homólogo Zeste 2/genética , Femenino , Humanos , Antígeno Ki-67/metabolismo , Receptor ErbB-2 , Receptores de Estrógenos/metabolismo , Estudios Retrospectivos
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