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1.
Front Plant Sci ; 13: 827478, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371125

RESUMO

Potassium (K) is an indispensable nutrient element in the development of fruit trees in terms of yield and quality. It is unclear how a stable or unstable supply of K affects plant growth. We studied the root morphology and physiological and molecular changes in the carbon and nitrogen metabolism of M9T337 apple rootstock under different K levels and supply methods using hydroponics. Five K supply treatments were implemented: continuous low K (KL), initial low and then high K (KLH), appropriate and constant K (KAC), initial high and then low K (KHL), and continuous high K (KH). The results showed that the biomass, root activity, photosynthesis, and carbon and nitrogen metabolism of the M9T337 rootstocks were inhibited under KL, KH, KLH and KHL conditions. The KAC treatment promoted root growth by optimizing endogenous hormone content, enhancing carbon and nitrogen metabolism enzyme activities, improving photosynthesis, optimizing the distribution of carbon and nitrogen, and upregulating the transcription levels of nitrogen assimilation-related genes (nitrate reductase, glutamine synthetase, glutamate synthase, MdNRT1.1, MdNRT1.2, MdNRT1.5, MdNRT2.4). These results suggest that an appropriate and constant K supply ensures the efficient assimilation and utilization of nitrogen and carbon.

2.
Front Neurol ; 13: 884460, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547369

RESUMO

Despite the ubiquity of the Boston naming test (BNT) in clinical practice and research, concerns have been expressed about its poor quality pictures, insufficient psychometric properties, and cultural bias in non-English language backgrounds. We modified the black-and-white BNT with a set of color pictures since color effects have been suggested to improve naming accuracy in the visual naming test. This study aimed to examine and compare the reliability and validity of the color-picture version of BNT (CP-BNT) and the black-and-white version of BNT (BW-BNT) to differentiate amnestic mild cognitive impairment (aMCI) or mild Alzheimer's disease (AD) from the cognitive normals. This study included two subgroups, and each subgroup had 101 normal controls, 51 aMCI, and 52 mild AD. One subgroup undertook BW-BNT and the other conducted CP-BNT. The reliability, convergent and discriminant validity, and the diagnostic accuracy of two versions of BNT were evaluated. The CP-BNT showed a greater area under the curve (AUC) than the BW-BNT for aMCI (80.3 vs.s 69.4%) and mild AD (93.5 vs. 77.6%). The CP-BNT also demonstrated better convergent validity with CDR global scores and better reliability (Cronbach's coefficient 0.66 for the CP-BNT vs. 0.55 for the BW-BNT). At the optimal cutoff value of spontaneous naming, the CP-BNT demonstrated improved sensitivity and specificity for differentiating mild AD from NC with a higher positive predictive value, negative predictive value, and lower false-positive rate. Compared with BW-BNT, CP-BNT is a more reliable and valid test to assess cognitive and naming impairment.

3.
J Nutr Biochem ; : 109041, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35568098

RESUMO

Indole is a microbiota metabolite that functions to protect against obesity-associated non-alcoholic fatty liver disease (NAFLD). The present study examined the extent to which indole supplementation alleviates the severity of non-alcoholic steatohepatitis (NASH), which is the advanced form of NAFLD. In C57BL/6J mice, feeding a methionine- and choline-deficient diet (MCD) resulted in significant weight loss, overt hepatic steatosis, and massive aggregations of macrophages in the liver compared with control diet-fed mice. Upon indole supplementation, the severity of MCD-induced hepatic steatosis and inflammation, as well as liver fibrosis, was significantly decreased compared with that of MCD-fed and control-treated mice. In vitro, indole treatment caused significant decreases in lipopolysaccharide (LPS)-induced proinflammatory responses in hepatocytes incubated with either basal or MCD-mimicking media. However, indole treatment only significantly decreased LPS-induced proinflammatory responses in bone marrow-derived macrophages incubated with basal, but not MCD-mimicking media. These differential effects suggest that, relative to the responses of macrophages to indole, the responses of hepatocytes to indole appeared to make a greater contribution to indole alleviation of NASH, in particular liver inflammation. While indole supplementation decreased liver expression of desmin in MCD-fed mice, treatment of LX2 cells (a line of hepatic stellate cells) with indole also decreased the expression of various markers of HSC fibrogenic activation. Lastly, indole supplementation decreased intestinal inflammation in MCD-fed mice, suggesting that decreased intestinal inflammation also was involved in indole alleviation of NASH. Collectively, these results demonstrate that indole supplementation alleviates MCD-induced NASH, which is attributable to, in large part, indole suppression of hepatocyte proinflammatory responses and HSC fibrogenic activation, as well as intestinal proinflammatory responses.

4.
Aging (Albany NY) ; 14(9): 4158-4175, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35550569

RESUMO

The development of cancer was determined by not only the intrinsic properties of cancer cells, but also the communication between cancer cells and tumor microenvironment (TME). We applied ESTIMATE and CIBERSORT algorithms to calculate the immune/stromal component and tumor-infiltrating immune cells (TICs) in TME of BC. The results showed that immune component in TME predicted patients' survival and associated with progression of BC. Differentially expressed genes (DEGs) were primarily enriched in immune-related activities. Finally, CCL19 was acquired which shared the leading nodes in PPI network and was associated with patients' survival. High expression of CCL19 predicted better prognosis and participated in progression of BC. Genes in CCL19 up-regulated group were enriched in immune-related activities and these functions might depend on the communications between CCL19 and multiple TICs in TIME. In conclusion, CCL19 functioned as a potential prognostic biomarker and a modulator of TIME in BC through communicating with various TICs.


Assuntos
Neoplasias da Mama , Microambiente Tumoral , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Quimiocina CCL19/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Microambiente Tumoral/genética
5.
BMC Neurosci ; 23(1): 25, 2022 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468730

RESUMO

BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune illness that renders individuals vulnerable to neuropsychopathology even in the euthyroid state, the mechanisms involved remain unclear. We hypothesized that activated microglia might disrupt synapses, resulting in cognitive disturbance in the context of euthyroid HT, and designed the present study to test this hypothesis. METHODS: Experimental HT model was induced by immunizing NOD mice with thyroglobulin and adjuvant twice. Morris Water Maze was measured to determine mice spatial learning and memory. The synaptic parameters such as the synaptic density, synaptic ultrastructure and synaptic-markers (SYN and PSD95) as well as the interactions of microglia with synapses were also determined. RESULTS: HT mice had poorer performance in Morris Water Maze than controls. Concurrently, HT resulted in a significant reduction in synapse density and ultrastructure damage, along with decreased synaptic puncta visualized by immunostaining with synaptophysin and PSD-95. In parallel, frontal activated microglia in euthyroid HT mice showed increased engulfment of PSD95 and EM revealed that the synaptic structures were visible within the microglia. These functional alterations in microglia corresponded to structural increases in their attachment to neuronal perikarya and a reduction in presynaptic terminals covering the neurons. CONCLUSION: Our results provide initial evidence that HT can induce synaptic loss in the euthyroid state with deficits might be attributable to activated microglia, which may underlie the deleterious effects of HT on spatial learning and memory.


Assuntos
Doença de Hashimoto , Microglia , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos NOD , Microglia/patologia , Sinapses
6.
Front Genet ; 13: 832331, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464857

RESUMO

Purpose: Mitochondrial dysfunction refers to cancer immune evasion. A novel 7-gene prognostic signature related to the mitochondrial DNA copy number was utilized to evaluate the immunocyte infiltration in colon cancer according to the risk scores and to predict the survival for colon cancer. Experimental design: We performed an integrated bioinformatic analysis to analyze transcriptome profiling of the EB-treated mitochondrial DNA-defected NCM460 cell line with differentially expressed genes between tumor and normal tissues of COAD in TCGA. The LASSO analysis was utilized to establish a prognostic signature. ESTIMATE and CIBERSORT validated the differences of immunocyte infiltration between colon cancer patients with high- and low-risk scores. Results: Our study identified a 7-gene prognostic signature (LRRN2, ANKLE1, GPRASP1, PRAME, TCF7L1, RAB6B, and CALB2). Patients with colon cancer were split into the high- and low-risk group by the risk scores in TCGA (training cohort: HR = 2.50 p < 0.0001) and GSE39582 (validation cohort: HR = 1.43 p < 0.05). ESTIMATE and CIBERSORT revealed diverseness of immune infiltration in the two groups, especially downregulated T-cell infiltration in the patients with high-risk scores. Finally, we validated the colon patients with a low expression of the mitochondrial number biomarker TFAM had less CD3+ and CD8+ T-cell infiltration in clinical specimens. Conclusion: An mtDNA copy number-related 7-gene prognostic signature was investigated and evaluated, which may help to predict the prognosis of colon cancer patients and to guide clinical immunotherapy via immunocyte infiltration evaluation.

7.
Eur J Pharmacol ; : 174954, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35421359

RESUMO

BACKGROUND: It is reported that the osteogenesis in bone marrow mesenchymal stem cells (BMSCs) can alleviate osteoporosis progression. It has been found that Kae can promote the osteogenesis in BMSCs. However, the mechanism by which Kae mediates the osteogenesis in BMSCs is largely unknown. METHODS: RBMSCs were collected from rats. The cytotoxicity of Kae was detected by CCK-8 assay. The osteogenic calcification in rBMSCs was measured by alizarin red staining, and ALP staining was performed to test the ALP activity in osteoblasts. The binding relationship between SOX2 and miR-124-3p was explored by dual luciferase report assay and Chromatin Immunoprecipitation (ChIP). RT-qPCR and western blot were performed to assess mRNA and protein levels, respectively. RESULTS: Kae (10 µM) significantly increased the calcification, ALP activity, SOX2 level, activated PI3K/Akt/mTOR signaling and inhibited miR-124-3p level in rBMSCs, while knockdown of SOX2 reversed this phenomenon. Meanwhile, SOX2 suppressed the transcription of miR-124-3p, and SOX2 promoted the osteogenic differentiation in rBMSCs via regulation of miR-124-3p. MiR-124-3p could inactivate PI3K/Akt/mTOR to inhibit the osteogenic differentiation. CONCLUSION: Kae significantly promoted the osteogenesis in rBMSCs via mediation of SOX2/miR-124-3p/PI3K/Akt/mTOR axis. Thus, our study might shed new lights in exploring new methods against osteoporosis.

8.
Front Pharmacol ; 13: 823975, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444554

RESUMO

Background: Doxorubicin (DOX)-induced cardiotoxicity is a highly concerning issue, and the mechanism by which DOX induces cardiotoxicity is likely to be multifactorial. NADPH oxidase (NOX) is associated with DOX-induced cardiotoxicity. Setanaxib (GKT137831), a preferential direct inhibitor of NOX1 and NOX4, can delay or prevent the progression of many cardiovascular disorders by inhibiting reactive oxygen species (ROS) generation. In this study, we investigated the role of GKT137831 in ameliorating DOX-induced cardiotoxicity and the potential mechanisms of its action. Methods and Results: The mice model of cardiotoxicity induced by DOX was established, and GKT137831 treatment was performed at the same time. Neonatal rat cardiomyocytes (NRCMs) were treated with DOX or GKT137831 for in vitro experiments. We found that DOX administration impaired cardiac function in vivo, reflected by decreased left ventricular ejection fraction (LVEF) and fractional shortening (FS%). DOX also impaired the viability of NRCMs in vitro. In addition, DOX increased the levels of NOX1 and NOX4 expression and ROS production and the cardiomyocyte apoptosis rate, both in vivo and in vitro. GKT137831 improved cardiac function, as indicated by the increased LVEF and FS%. In vitro, GKT137831 improved NRCM viability. It also decreased ROS production and the cardiomyocyte apoptosis rate. Apoptotic indices, such as cleaved PARP (c-PARP), cleaved caspase 3 (CC3) and BAX expression levels, were decreased, and the antiapoptotic index of Bcl-2 expression was increased. DOX markedly activated phosphorylated JNK, ERK and p38 proteins in NRCMs. Specific inhibitors of JNK (SP600125), ERK (PD98059) or p38 (SB203580) inhibited DOX-induced apoptosis of NRCMs. GKT137831 pretreatment inhibited excessive DOX-induced MAPK pathway activation. Conclusion: This study revealed that GKT137831 can alleviate DOX-induced cardiomyocyte apoptosis by inhibiting NOX1/4-driven ROS production. The upregulation of MAPK pathway induced by NOX1/4-derived ROS production may be the potential mechanism of GKT137831 action. GKT137831 may be a potential drug candidate to ameliorate DOX-induced cardiotoxicity.

9.
Antimicrob Agents Chemother ; 66(5): e0222421, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35400177

RESUMO

The cycloserine concentrations in plasma and bone that were collected during operations on 28 osteoarticular tuberculosis (TB) patients treated daily with a 500-mg cycloserine-containing regimen were determined. The median concentrations in plasma and bone were 16.29 µg/mL (interquartile range [IQR], 6.47 µg/mL) and 24.33 µg/g (IQR, 14.68 µg/g), respectively. The median bone/plasma penetration ratio was 0.76 (range, 0.33 to 1.98). Cycloserine could effectively penetrate bone and acquire concentrations comparable to those in plasma, which favors its usage in osteoarticular TB treatment.

10.
ACS Omega ; 7(14): 12089-12097, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35449915

RESUMO

Biomimetic synthesis of amorphous photonic crystals (APCs) is an effective approach to obtaining non-iridescent structural colors. However, the structural colors of artificially prepared APCs are dim or even white due to the influence of incoherent scattering. In this paper, we present a novel method to combine APCs with black TiO2-x to construct a noniridescent structural color pigments with high visibility and photocatalytic activity. Due to the absorption of incoherently scattered light by black TiO2-x , the color saturation of structural colors has been significantly increased. In addition, the utilization rate of photogenic carriers was effectively enhanced by the slow light effect generated from the pseudoband gap of SiO2 APCs with TiO2-x absorbed full spectrum. The tone and color saturation of catalytic pigments is controlled by the diameter of SiO2 nanospheres and the ratio of TiO2-x nanoparticles, which provides a controllable application study in color-related fields as artwork, environmental coatings, and textiles.

11.
Sci Transl Med ; 14(641): eabl8146, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35442706

RESUMO

Asthma and inflammatory airway diseases restrict airflow in the lung, compromising gas exchange and lung function. Inhaled corticosteroids (ICSs) can reduce inflammation, control symptoms, and improve lung function; however, a growing number of patients with severe asthma do not benefit from ICS. Using bronchial airway epithelial brushings from patients with severe asthma or primary human cells, we delineated a corticosteroid-driven fibroblast growth factor (FGF)-dependent inflammatory axis, with FGF-responsive fibroblasts promoting downstream granulocyte colony-stimulating factor (G-CSF) production, hyaluronan secretion, and neutrophilic inflammation. Allergen challenge studies in mice demonstrate that the ICS, fluticasone propionate, inhibited type 2-driven eosinophilia but induced a concomitant increase in FGFs, G-CSF, hyaluronan, and neutrophil infiltration. We developed a model of steroid-induced neutrophilic inflammation mediated, in part, by induction of an FGF-dependent epithelial-mesenchymal axis, which may explain why some individuals do not benefit from ICS. In further proof-of-concept experiments, we found that combination therapy with pan-FGF receptor inhibitors and corticosteroids prevented both eosinophilic and steroid-induced neutrophilic inflammation. Together, these results establish FGFs as therapeutic targets for severe asthma patients who do not benefit from ICS.


Assuntos
Asma , Fatores de Crescimento de Fibroblastos , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Animais , Fluticasona/farmacologia , Fluticasona/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Ácido Hialurônico , Inflamação/tratamento farmacológico , Camundongos
13.
Org Lett ; 24(13): 2531-2535, 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35354287

RESUMO

Reported herein is the efficient and atroposelective construction of two categories of C-N atropisomers via rhodium(III)-catalyzed C-H activation of sulfoxonium ylides en route to [4+2] annulation with sterically hindered, electron-rich alkynes. This reaction proceeds with high regio- and enantioselectivity under redox-neutral conditions via a double-substrate activation strategy, providing a novel entry to C-N axially chiral 4-functionalized 1-naphthols.

14.
Sci Total Environ ; 827: 154301, 2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-35257763

RESUMO

A lab-scale sulfur-limestone based bioretention system with a submerged zone was used to remove nitrate-nitrogen (NO3--N) from stormwater. The results indicated that denitrification mainly occurred during the first 5 d of drying period. With the NO3--N concentration in the influent increasing from 20 to 50 mg/L, after 5 d of drying period 93.99-97.26% NO3--N was removed, and the effluent sulfate (SO42-) concentration ranged from 170.28 to 359.87 mg/L. When the NO3--N content in the influent was lower than 30 mg/L, the effluent SO42- concentration met the Chinese Quality Standard for Ground Water (GB/T 14848-2017). Compared with the woodchips bioretention, there was no organic matter leakage problem. Sulfur autotrophic denitrification process followed first-order kinetic model, and the reaction kinetic parameters (k) were 0.7392-1.1472 d-1. The dominant genera in the submerged zone were Thiobacillus and Halothiobacillus (>63.69%) which participated in the sulfur autotrophic denitrification process.


Assuntos
Microbiota , Nitrogênio , Reatores Biológicos , Carbonato de Cálcio , Desnitrificação , Nitratos , Enxofre
15.
Front Neurol ; 13: 827945, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250831

RESUMO

Social cognition impairment has been recognized as an early and characteristic change in behavioral variant frontotemporal dementia (bvFTD). The Mini Social Cognition and Emotional Assessment (mini-SEA) is a clinical tool to rapidly evaluate social cognition. In this study, we explored the diagnostic value of social cognition by assessing the Chinese version of the mini-SEA and other standard neuropsychological tests in 22 patients with mild bvFTD, 26 patients with mild Alzheimer's disease (AD), including mild cognitive impairment (MCI) and mild dementia, and 30 control subjects. The discriminatory powers of these tests were evaluated and compared using the receiver operating characteristic curve (ROC). The mini-SEA scores of the bvFTD patients were significantly lower than those of the controls (Z = -6.850, adjusted P < 0.001) and AD patients (Z = -3.737, adjusted P = 0.001). ROC analysis showed that the mini-SEA had a high discriminatory power for differentiating bvFTD from the controls, with an area under the curve (AUC) value of 0.989 (95% CI = 0.905-1.000, P < 0.001). The AUC value of the mini-SEA for differentiating bvFTD from AD was 0.899 (95% CI = 0.777-0.967, P < 0.001), higher than that of the Auditory Verbal Learning Test Delayed Recall (AUC = 0.793), Boston Naming Test (AUC = 0.685) or Frontal Assessment Battery (AUC = 0.691). The Chinese version of mini-SEA is a good clinical tool for the early diagnosis of bvFTD, and has a high sensitivity and specificity to discriminate bvFTD from AD.

16.
Artigo em Inglês | MEDLINE | ID: mdl-35357043

RESUMO

The objective of this experiment is to evaluate the effects of yeast culture (YC) supplementation on blood characteristics, body size, carcass characteristics, organ weights, intestinal morphology, and enzyme activities. Five groups of geese were randomly assigned to five dietary treatments: the basal diet (control) and basal diets plus 0.5%, 1.0%, 2.0%, or 4.0% YC. Compared with the controls, YC supplementation at 0.5% and 1.0% increased the serum total protein (TP), albumin (ALB), and globulin (GLO) and decreased the uric acid and creatine kinase (CK) contents (p < 0.05). YC supplementation at 2.0% and 4.0% increased the CK, growth hormone, catalase and glutathione reductase contents, and relative proventriculus weights, and decreased the TP, ALB, and GLO contents, relative liver, gizzard, jejunum, ileum, and thymus weights (p < 0.05). YC supplementation at 2.0% improved fossil bone length, breast muscle percentage, jejunal villus height, ileal and jejunal villus height/crypt depth ratios, pepsin, lipase, amylase and pancreatic trypsin activities, and decreased abdominal fat percentage (p < 0.05). Furthermore, YC inclusion increased the body slope length (linear, p = 0.002; quadratic, p = 0.02), breast width (quadratic, p = 0.02), ileal (linear, p = 0.04; quadratic, p = 0.01) and duodenal villus height (cubic, p = 0.04), and decreased the relative gizzard (quadratic, p = 0.04) and thymus (linear, p = 0.002; quadratic, p = 0.02; cubic, p = 0.02) weights, liver (linear, p = 0.002; quadratic, p = 0.02), and serum (linear, p = 0.006; quadratic, p = 0.03) malondialdehyde contents, and jejunal crypt depth (quadratic, p = 0.03). The findings indicated that the YC supplementation had a positive effect on the growth and development of geese, with 2% YC being the most effective.

17.
J Immunother Cancer ; 10(2)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35140113

RESUMO

BACKGROUNDS: Immunotherapy is less effective in patients with epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancer (NSCLC). Lower programmed cell death-ligand 1 (PD-L1) expression and tumor mutation burden (TMB) are reported to be the underlying mechanism. Being another important factor to affect the efficacy of immunotherapy, tumor microenvironment (TME) characteristics of this subgroup of NSCLC are not comprehensively understood up to date. Hence, we initiated this study to describe the specific TME of EGFR-mutant lung adenocarcinoma (LUAD) from cellular compositional and functional perspectives to better understand the immune landscape of this most common subtype of NSCLC. METHODS: We used single-cell transcriptome sequencing and multiplex immunohistochemistry to investigate the immune microenvironment of EGFR-mutant and EGFR wild-type LUADs and determined the efficacy of immunotherapy. We analyzed single cells from nine treatment-naïve samples and compared them to three post-immunotherapy samples previously reported from single cell perspective using bioinformatics methods. RESULTS: We found that EGFR-mutant malignant epithelial cells had similar characteristics to the epithelial cells in non-responders. EGFR-mutant LUAD lacked CD8+ tissue-resident memory (TRM) cells, which could promote tertiary lymphoid structure generation by secreting CXCL13. In addition, other cell types, including tumor-associated macrophages and cancer-associated fibroblasts, which are capable of recruiting, retaining, and expanding CD8+ TRM cells in the TME, were also deficient in EGFR-mutant LUAD. Furthermore, EGFR-mutant LUAD had significantly less crosstalk between T cells and other cell types via programmed cell death-1 (PD-1) and PD-L1 or other immune checkpoints compared with EGFR wild-type LUAD. CONCLUSIONS: Our findings provide a comprehensive understanding of the immune landscape of EGFR-mutant LUAD at the single-cell level. Based on the results, many cellular components might have negative impact on the specific TME of EGFR-mutant LUAD through influencing CD8+ TRM. Lack of CD8+ TRM might be a key factor responsible for the suppressive TME of EGFR-mutant LUAD.


Assuntos
Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/metabolismo , Receptores ErbB/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias Pulmonares/genética , Análise de Célula Única/métodos , Transcriptoma/genética , Adenocarcinoma de Pulmão/patologia , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Pulmonares/patologia , Masculino , Mutação , Prognóstico , Microambiente Tumoral
18.
J Pathol ; 257(1): 53-67, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35043389

RESUMO

Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare renal epithelial neoplasm resembling type 1 papillary renal cell carcinoma (PRCC) morphologically and immunohistochemically. The accurate diagnosis of MTSCC remains a challenge. Here, by using proteomic profiling, we characterized MTSCC and PRCC to identify diagnostic biomarkers. We found that the MTSCC tumor proteome was significantly enriched in B-cell-mediated immunity when compared with the proteome of adjacent normal tissues of MTSCC or tumors of PRCC. Importantly, we identified MZB1, VCAN, and SOSTDC1 as diagnostic biomarkers to distinguish MTSCC from the solid variant of type 1 PRCC, with an AUC of 0.985 when combined. MZB1 was inversely correlated with tumor clinical stage and may play an anti-tumor role by activating the complement system. Finally, unsupervised clustering revealed two molecular subtypes of MTSCC, displaying different morphology, expression signatures of oxidative phosphorylation, and aggravation. In summary, our analyses identified a three-protein diagnostic panel and molecular subtypes for MTSCC. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Adenocarcinoma Mucinoso , Carcinoma de Células Renais , Neoplasias Renais , Proteínas Adaptadoras de Transdução de Sinal , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/patologia , Biomarcadores , Biomarcadores Tumorais/análise , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Humanos , Rim/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Proteoma , Proteômica
19.
Angew Chem Int Ed Engl ; 61(13): e202114346, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35007393

RESUMO

In this study, we systematically evaluate different ambiphilic organohalides for their ability to participate in anti-selective carbo- or heteroannulation with non-conjugated alkenyl amides under PdII /PdIV catalysis. Detailed optimization of the reaction conditions has led to protocols for synthesizing tetrahydropyridines, tetralins, pyrrolidines, and other carbo/heterocyclic cores via [n+2] (n=3-5) (hetero)annulation. Expansion of scope to otherwise unreactive ambiphilic haloketones through PdII /amine co-catalysis is also demonstrated. Compared to other annulation processes, this method proceeds via a distinct PdII /PdIV mechanism involving Wacker-type directed nucleopalladation. This difference results in unique reactivity and selectivity patterns, as revealed through assessment of reaction scope and competition experiments.


Assuntos
Alcenos , Paládio , Catálise , Pirrolidinas
20.
Int J Cancer ; 150(9): 1525-1536, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-34985768

RESUMO

The acquisition of ectopic type I fibroblast growth factor receptor (FGFR1) is a common feature of prostate cancer (PCa), the most frequently diagnostic cancer in men. However, how ectopic FGFR1 contributes to PCa progression is not well understood. In our study we showed that ablation of FGFR1 in DU145 human PCa cells changed the cell metabolite profile. Among the changes, the choline metabolism profile was the most significantly altered by FGFR1 ablation. Detailed characterization revealed that ablation of FGFR1 altered expression of multiple choline metabolism enzymes. Among the changes of FGFR1-regulated choline metabolic enzymes, downregulation of choline kinase α (CHKA) is the most prominent changes, which phosphorylates free choline to phosphocholine. Ablation of FGFR1 blunted the activity of choline to promote cell proliferation and survival. Furthermore, depletion of CHKA compromised FGF signaling activity in DU145 cells. We also first time demonstrated that FGFR1 formed complex with CHKA, suggesting that FGFR1 regulated CHKA at the posttranslational level. Together with the previous report that ectopic FGFR1 contributes to PCa progression and metastasis, our results here unravel a novel mechanism by which FGFR1 promotes PCa progression by dysregulating choline metabolism, and that the crosstalk between FGFR1-choline metabolism can be a potential target for managing PCa progression.


Assuntos
Colina , Neoplasias da Próstata , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Linhagem Celular Tumoral , Proliferação de Células , Colina/metabolismo , Humanos , Masculino , Próstata/patologia , Neoplasias da Próstata/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais
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