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1.
Front Neurol ; 13: 812458, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35677331

RESUMO

Stent retriever thrombectomy (SRT) is one of the most effective methods for the recanalization of acute basilar artery occlusion (ABAO). The proatlantal intersegmental artery (PIA) is a rare carotid-vertebrobasilar anastomosis. Recognition of this rare form of anastomosis is particularly important for the rapid establishment of positive blood flow in patients with ABAO. In this case, the patient had a rare, left type 1 PIA. The right vertebral artery (VA) was tenuous and did not enter the cranium. We performed a thrombectomy of the ABAO by inserting a catheter via the type 1 PIA. The complete recanalization of basilar artery (BA) flow was achieved following two stent retractions; however, the patient eventually died of brain stem hemorrhage.

2.
Microb Cell Fact ; 21(1): 97, 2022 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-35643494

RESUMO

BACKGROUND: Carbamate pesticides have been widely used in agricultural and forestry pest control. The large-scale use of carbamates has caused severe toxicity in various systems because of their toxic environmental residues. Carbaryl is a representative carbamate pesticide and hydrolase/carboxylesterase is the initial and critical enzyme for its degradation. Whole-cell biocatalysts have become a powerful tool for environmental bioremediation. Here, a whole cell biocatalyst was constructed by displaying a novel carboxylesterase/hydrolase on the surface of Escherichia coli cells for carbaryl bioremediation. RESULTS: The carCby gene, encoding a protein with carbaryl hydrolysis activity was cloned and characterized. Subsequently, CarCby was displayed on the outer membrane of E. coli BL21(DE3) cells using the N-terminus of ice nucleation protein as an anchor. The surface localization of CarCby was confirmed by SDS-PAGE and fluorescence microscopy. The optimal temperature and pH of the engineered E. coli cells were 30 °C and 7.5, respectively, using pNPC4 as a substrate. The whole cell biocatalyst exhibited better stability and maintained approximately 8-fold higher specific enzymatic activity than purified CarCby when incubated at 30 °C for 120 h. In addition, ~ 100% and 50% of the original activity was retained when incubated with the whole cell biocatalyst at 4 ℃ and 30 °C for 35 days, respectively. However, the purified CarCby lost almost 100% of its activity when incubated at 30 °C for 134 h or 37 °C for 96 h, respectively. Finally, approximately 30 mg/L of carbaryl was hydrolyzed by 200 U of the engineered E. coli cells in 12 h. CONCLUSIONS: Here, a carbaryl hydrolase-containing surface-displayed system was first constructed, and the whole cell biocatalyst displayed better stability and maintained its catalytic activity. This surface-displayed strategy provides a new solution for the cost-efficient bioremediation of carbaryl and could also have the potential to be used to treat other carbamates in environmental bioremediation.


Assuntos
Escherichia coli , Praguicidas , Biodegradação Ambiental , Carbaril/metabolismo , Carboxilesterase/genética , Carboxilesterase/metabolismo , Escherichia coli/metabolismo , Praguicidas/metabolismo
3.
Cell Death Dis ; 13(5): 505, 2022 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-35643812

RESUMO

The use of PARP inhibitors in combination with radiotherapy is a promising strategy to locally enhance DNA damage in tumors. Loss of XRCC2 compromises DNA damage repairs, and induced DNA damage burdens may increase the reliance on PARP-dependent DNA repairs of cancer cells to render cell susceptibility to PARP inhibitor therapy. Here we tested the hypothesis that XRCC2 loss sensitizes colorectal cancer (CRC) to PARP inhibitor in combination with radiotherapy (RT). We show that high levels of XRCC2 or PARP1 in LARC patients were significantly associated with poor overall survival (OS). Co-expression analyses found that low levels of PARP1 and XRCC2 were associated with better OS. Our in vitro experiments indicated that olaparib+IR led to reduced clonogenic survival, more DNA damage, and longer durations of cell cycle arrest and senescence in XRCC2-deficient cells relative to wild-type cells. Furthermore, our mouse xenograft experiments indicated that RT + olaparib had greater anti-tumor effects and led to long-term remission in mice with XRCC2-deficient tumors. These findings suggest that XRCC2-deficient CRC acquires high sensitivity to PARP inhibition after IR treatment and supports the clinical development for the use of olaparib as a radiosensitizer for treatment of XRCC2-deficient CRC.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/radioterapia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/uso terapêutico , Humanos , Camundongos , Ftalazinas/farmacologia , Ftalazinas/uso terapêutico , Piperazinas , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
5.
Neurotherapeutics ; 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35764763

RESUMO

The motor protein Eg5, known as kif11 or kinesin-5, interacts with adjacent microtubules in the mitotic spindle and plays essential roles in cell division, yet the function of Eg5 in mature postmitotic neurons remains largely unknown. In this study, we investigated the contribution and molecular mechanism of Eg5 in pathological pain. Pharmacological inhibition of Eg5 and a specific shRNA-expressing viral vector reversed complete Freund's adjuvant (CFA)-induced pain and abrogated vanilloid receptor subtype 1 (VR1) expression in dorsal root ganglion (DRG) neurons. In the dorsal root, Eg5 inhibition promoted VR1 axonal transport and decreased VR1 expression. In the spinal cord, Eg5 inhibition suppressed VR1 expression in axon terminals and impaired synapse formation in superficial laminae I/II. Finally, we showed that Eg5 is necessary for PI3K/Akt signalling-mediated VR1 membrane trafficking and pathological pain. The present study provides compelling evidence of a noncanonical function of Eg5 in primary sensory neurons. These results suggest that Eg5 may be a potential therapeutic target for intractable pain.

6.
Evol Appl ; 15(4): 603-617, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35505885

RESUMO

To meet human needs, domestic pigeons (Columba livia) with various phenotypes have been bred to provide genetic material for our research on artificial selection and local environmental adaptation. Seven pigeon breeds were resequenced and can be divided into commercial varieties (Euro-pigeon, Shiqi, Shen King, Taishen, and Silver King), ornamental varieties (High Fliers), and local varieties (Tarim pigeon). Phylogenetic analysis based on population resequencing showed that one group contained local breeds and ornamental pigeons from China, whereas all commercial varieties were clustered together. It is revealed that the traditional Chinese ornamental pigeon is a branch of Tarim pigeon. Runs of homozygosity (ROH) and linkage disequilibrium (LD) analyses revealed significant differences in the genetic diversity of the three types of pigeons. Genome sweep analysis revealed that the selected genes of commercial breeds were related to body size, reproduction, and plumage color. The genomic imprinting genes left by the ornamental pigeon breeds were mostly related to special human facial features and muscular dystrophy. The Tarim pigeon has evolved genes related to chemical ion transport, photoreceptors, oxidative stress, organ development, and olfaction in order to adapt to local environmental stress. This research provides a molecular basis for pigeon genetic resource evaluation and genetic improvement and suggests that the understanding of adaptive evolution should integrate the effects of various natural environmental characteristics.

7.
Neurochem Res ; 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522367

RESUMO

Satellite glial cells (SGCs) tightly surround neurons and modulate sensory transmission in dorsal root ganglion (DRG). At present, the biological property of primary SGCs in culture deserves further investigation. To reveal the key factor for SGCs growth and survival, we examined the effects of different culture supplementations containing Dulbecco's Modified Eagle Medium (DMEM)/F12, DMEM high glucose (HG) or Neurobasal-A (NB). CCK-8 proliferation assay showed an increased proliferation of SGCs in DMEM/F12 and DMEM/HG, but not in NB medium. Bax, AnnexinV, and propidium iodide (PI) staining results showed that NB medium caused cell death and apoptosis. We showed that glutamine was over 2.5 mM in DMEM/F12 and DMEM/HG, whereas it was absence in NB medium. Interestingly, exogenous glutamine application significantly reversed the poor proliferation and cell death of SGCs in NB medium. These findings demonstrated that DMEM/F12 medium was optimal to get high-purity SGCs. Glutamine was the key molecule to maintain SGCs growth and survival in culture. Here, we provided a novel approach to get high-purity SGCs by changing the key component of culture medium. Our study shed a new light on understanding the biological property and modulation of glial cells of primary sensory ganglia.

9.
ACS Macro Lett ; 11(5): 669-674, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35570809

RESUMO

The knowledge of chain entanglement is key to our understanding of the relation between the viscoelastic properties of polymeric material and their microscopic structure and dynamics. This work conducted a detailed study on the role of short chains in the entangled polymer network. A series of poly(ethylene oxide) (PEO) mixtures with bimodal molecular weight distribution were selected for this study. 1H double-quantum (DQ) NMR combined with the rheology measurement was used to investigate the entangled polymer network. We found that short-chain polymers have the potential to significantly alter the entangled polymer network formed by long-chain polymers. Additionally, both the amount of chain ends and the size of the short-chain polymer were found to have clear disentanglement influences on the entangled polymer network. Moreover, adding low molecular weight PEO to the entangle framework formed by the high molecular weight PEO, resulted in the formation of inhomogeneous entangled polymer networks. The effect of low molecular weight polymers on the entangled polymer networks in PEO melts provides a perspective on the molecular level effect of molecular weight distribution (MWD) on entanglement polymer networks.

10.
Plant Commun ; 3(2): 100268, 2022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-35529951

RESUMO

Gene duplication provides raw genetic materials for evolution and potentially novel genes for crop improvement. The two seminal genomic studies of Aegilops tauschii both mentioned the large number of genes independently duplicated in recent years, but the duplication mechanism and the evolutionary significance of these gene duplicates have not yet been investigated. Here, we found that a recent burst of gene duplications (hereafter abbreviated as the RBGD) has probably occurred in all sequenced Triticeae species. Further investigations of the characteristics of the gene duplicates and their flanking sequences suggested that transposable element (TE) activity may have been involved in generating the RBGD. We also characterized the duplication timing, retention pattern, diversification, and expression of the duplicates following the evolution of Triticeae. Multiple subgenome-specific comparisons of the duplicated gene pairs clearly supported extensive differential regulation and related functional diversity among such pairs in the three subgenomes of bread wheat. Moreover, several duplicated genes from the RBGD have evolved into key factors that influence important agronomic traits of wheat. Our results provide insights into a unique source of gene duplicates in Triticeae species, which has increased the gene dosage together with the two polyploidization events in the evolutionary history of wheat.


Assuntos
Aegilops , Duplicação Gênica , Aegilops/genética , Genoma de Planta/genética , Poaceae/genética , Triticum/genética
11.
Cells ; 11(10)2022 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-35626749

RESUMO

Identifying effective donor cells is one of obstacles that limits cell therapy for heart disease. In this study, we sorted a subpopulation of human mesenchymal progenitor cells (hMPCs) from the right atrial appendage using the low mitochondrial membrane potential. Compared to the non-sorted cells, hMPCs hold the capacity for stemness and enrich mesenchymal stem cell markers. The hMPCs display better ability for survival, faster proliferation, less production of reactive oxygen species (ROS), and greater release of cytoprotective cytokines. The hMPCs exhibit decreased expression of senescence genes and increased expression of anti-apoptotic and antioxidant genes. Intramyocardial injection of hMPCs into the infarcted heart resulted in increased left ventricular ejection fraction and reduced cardiac remodeling and infarct size in the group of animals receiving hMPCs. Both in vitro and in vivo studies indicated hMPCs have the potential to differentiate into endothelial cells and smooth muscle cells. Immunohistochemistry staining showed that cell therapy with hMPCs enhances cardiac vascular regeneration and cardiac proliferation, and decreases cardiac cell apoptosis, which is associated with the increased secretion of cytoprotective and pro-angiogenic cytokines. Overall, we discovered a subpopulation of human mesenchymal progenitor cells via their low mitochondrial membrane potential, which might provide an alternative donor cell source for cellular therapy for ischemic heart disease.


Assuntos
Células Endoteliais , Células-Tronco Mesenquimais , Animais , Citocinas/metabolismo , Células Endoteliais/metabolismo , Potencial da Membrana Mitocondrial , Células-Tronco Mesenquimais/metabolismo , Neovascularização Patológica/metabolismo , Volume Sistólico , Função Ventricular Esquerda
12.
JNCI Cancer Spectr ; 6(2)2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35603847

RESUMO

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) treated in real-world practice typically have worse performance status (PS) compared with clinical trial patients, and the effectiveness of immunotherapy in this population in unknown. In this study, we assessed the effectiveness of standard of care immunotherapy for the first-line treatment of stage IV patients with NSCLC with Eastern Cooperative Oncology Group (ECOG) PS greater than or equal to 2. METHODS: We selected ECOG PS greater than or equal to 2 patients from real-world oncology data from a deidentified database and included them if they were diagnosed with stage IV NSCLC and had documented Programmed death-ligand 1 [PD-(L)1] expression greater than 0. Patients with tumor PD-(L)1 expression of at least 50% treated with pembrolizumab monotherapy were compared with those who did not have any documented treatment. Patients with tumor PD-(L)1 expression less than 50% treated with pembrolizumab and chemotherapy were compared with those treated with pembrolizumab monotherapy and those without documented treatment. RESULTS: In our propensity score-adjusted analysis, patients with ECOG PS of at least 2 and tumor PD-(L)1 expression of at least 50% treated with pembrolizumab monotherapy had statistically significantly better real-world overall survival compared with those without documented treatment (adjusted hazard ratio [HR] = 0.39, 95% confidence internal [CI] = 0.32 to 0.47). For patients with tumor PD-(L)1 expression less than 50%, there was also a statistically significant real-world overall survival benefit for those who received treatment either with combination pembrolizumab plus chemotherapy (adjusted HR = 0.39, 95% CI = 0.32 to 0.46) or pembrolizumab monotherapy (adjusted HR = 0.55, 95% CI = 0.41 to 0.70) compared with patients receiving no documented treatment. CONCLUSIONS: Among a highly representative sample of patients with advanced NSCLC and poor PS, our findings suggest that immunotherapy may provide an important survival benefit in individuals with high PD-(L)1-expressing tumors and in conjunction with chemotherapy in tumors with low PD-(L)1 expression.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico
13.
Front Plant Sci ; 13: 847863, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35557725

RESUMO

Rice is a salt-sensitive plant. High concentration of salt will hinder the absorption of water and nutrients and ultimately affect the yield. In this study, eight seedling-stage salt-related traits within a core collection of rice landraces were evaluated under salinity stress (100 mM NaCl) and normal conditions in a growth chamber. Genome-wide association study (GWAS) was performed with the genotypic data including 2,487,353 single-nucleotide polymorphisms (SNPs) detected in the core collection. A total of 65 QTLs significantly associated with salt tolerance (ST) were identified by GWAS. Among them, a co-localization QTL qTL4 associated with the SKC, RN/K, and SNC on chromosome 6, which explained 14.38-17.94% of phenotypic variation, was selected for further analysis. According to haplotype analysis, qRT-PCR analysis, and sequence alignment, it was finally determined that 4 candidate genes (LOC_Os06g47720, LOC_Os06g47820, LOC_Os06g47850, LOC_Os06g47970) were related to ST. The results provide useful candidate genes for marker assisted selection for ST in the rice molecular breeding programs.

14.
Polymers (Basel) ; 14(8)2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35458271

RESUMO

Understanding the structural evolution process after the yielding of networks in polymer nanocomposites can provide significant insights into the design and fabrication of high-performance nanocomposites. In this work, using hydroxyl-terminated 1,4-polybutadiene (HTPB)/organo-clay nanocomposite gel as a model, we explored the yielding and recovery process of a polymer network. Linear rheology results revealed the formation of a nanocomposite gel with a house-of-cards structure due to the fully exfoliated 6 to 8 wt% organo-clays. Within this range, nonlinear rheologic experiments were introduced to yield the gel network, and the corresponding recovery processes were monitored. It was found that the main driving force of network reconstruction was the polymer-clay interaction, and the rotation of clay sheets played an important role in arousing stress overshoots. By proton double-quantum (1H DQ) NMR spectroscopy, residual dipolar coupling and its distribution contributed by HTPB segments anchored on clay sheets were extracted to unveil the physical network information. During the yielding process of a house-of-cards network, e.g., 8 wt% organo-clay, nearly one-fourth of physical cross-linking was broken. Based on the rheology and 1H DQ NMR results, a tentative model was proposed to illustrate the yielding and recovery of the network in HTPB/organo-clay nanocomposite gel.

15.
Cancer Epidemiol Biomarkers Prev ; 31(4): 704-706, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35373264

RESUMO

In the past decades, multigene prognostic testing, such as Oncotype DX (ODX), has been increasingly used to inform treatment decisions for patients with early-stage breast cancer. This advance in precision oncology has increased existing concerns about differential access to genomic testing across racial and ethnic groups. The investigation by Moore and colleagues, analyzing real-world data from the National Cancer Database, shows that patients of color with breast cancer were less likely to receive ODX testing and Black patients were more likely to have a high risk Recurrence Score (RS) compared with White patients. This study emphasizes that the appropriate adoption of ODX testing is critical to promote equitable cancer care for patients with breast cancer. The reported associations on overall survival across specific racial and ethnic groups provided here give additional insight to the known associations between the ODX RS and outcomes of distant recurrence and cancer-specific mortality. Analyses of contemporary, real-world data from diverse populations with long-term follow-up should continue to keep pace with the expansion of precision breast cancer care to better understand and mitigate potentially widening inequities in genomic testing. See related article by Moore et al., p. 821.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/etnologia , Feminino , Perfilação da Expressão Gênica , Humanos , Medicina de Precisão , Prognóstico
16.
Sci Rep ; 12(1): 6199, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35418701

RESUMO

Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values < 5 × 10-8 as genome-wide significant, and p-values < 1 × 10-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants. None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values < 1 × 105. The strongest evidence was found for rs4674019 (p-value = 2.27 × 10-7), which showed genome-wide significant interaction (p-value = 3.8 × 10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT-breast cancer risk association.


Assuntos
Neoplasias da Mama , Mama , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Masculino , Menopausa , Fatores de Risco
17.
CNS Neurosci Ther ; 28(7): 1108-1123, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35445545

RESUMO

AIMS: dl-PHPB (potassium 2-(1-hydroxypentyl)-benzoate) has been shown to have neuroprotective effects against acute cerebral ischemia, vascular dementia, and Alzheimer's disease. The aim of this study was to investigate the effects of dl-PHPB on memory deficits and preliminarily explore the underlying molecular mechanism. METHODS: Blood glucose and behavioral performance were evaluated in the KK-Ay diabetic mouse model before and after dl-PHPB administration. Two-dimensional difference gel electrophoresis (2D-DIGE)-based proteomics was used to identify differentially expressed proteins in brain tissue. Western blotting was used to study the molecular mechanism of the related signaling pathways. RESULTS: Three-month-old KK-Ay mice were given 150 mg/kg dl-PHPB by oral gavage for 2 months, which produced no effect on the level of serum glucose. In the Morris water maze test, KK-Ay mice treated with dl-PHPB showed significant improvements in spatial learning and memory deficits compared with vehicle-treated KK-Ay mice. Additionally, we performed 2D-DIGE to compare brain proteomes of 5-month KK-Ay mice treated with and without dl-PHPB. We found 14 altered proteins in the cortex and 11 in the hippocampus; two of the 25 altered proteins and another four proteins that were identified in a previous study on KK-Ay mice were then validated by western blot to further confirm whether dl-PHPB can reverse the expression levels of these proteins. The phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase-3ß (PI3K/Akt/GSK-3ß) signaling pathway was also changed in KK-Ay mice and dl-PHPB treatment could reverse it. CONCLUSIONS: These results indicate that dl-PHPB may play a potential role in diabetes-associated cognitive impairment through PI3K/Akt/GSK-3ß signaling pathway and the differentially expressed proteins may become putative therapeutic targets.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus , Animais , Benzoatos , Encéfalo/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Modelos Animais de Doenças , Glicogênio Sintase Quinase 3 beta/metabolismo , Transtornos da Memória/metabolismo , Camundongos , Pentanos , Fosfatidilinositol 3-Quinases/metabolismo , Potássio , Proteômica , Proteínas Proto-Oncogênicas c-akt/metabolismo
18.
Stem Cells ; 40(2): 133-148, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35257186

RESUMO

The N-terminal caveolin-binding motif (CBM) in Na/K-ATPase (NKA) α1 subunit is essential for cell signaling and somitogenesis in animals. To further investigate the molecular mechanism, we have generated CBM mutant human-induced pluripotent stem cells (iPSCs) through CRISPR/Cas9 genome editing and examined their ability to differentiate into skeletal muscle (Skm) cells. Compared with the parental wild-type human iPSCs, the CBM mutant cells lost their ability of Skm differentiation, which was evidenced by the absence of spontaneous cell contraction, marker gene expression, and subcellular myofiber banding structures in the final differentiated induced Skm cells. Another NKA functional mutant, A420P, which lacks NKA/Src signaling function, did not produce a similar defect. Indeed, A420P mutant iPSCs retained intact pluripotency and ability of Skm differentiation. Mechanistically, the myogenic transcription factor MYOD was greatly suppressed by the CBM mutation. Overexpression of a mouse Myod cDNA through lentiviral delivery restored the CBM mutant cells' ability to differentiate into Skm. Upstream of MYOD, Wnt signaling was demonstrated from the TOPFlash assay to have a similar inhibition. This effect on Wnt activity was further confirmed functionally by defective induction of the presomitic mesoderm marker genes BRACHYURY (T) and MESOGENIN1 (MSGN1) by Wnt3a ligand or the GSK3 inhibitor/Wnt pathway activator CHIR. Further investigation through immunofluorescence imaging and cell fractionation revealed a shifted membrane localization of ß-catenin in CBM mutant iPSCs, revealing a novel molecular component of NKA-Wnt regulation. This study sheds light on a genetic regulation of myogenesis through the CBM of NKA and control of Wnt/ß-catenin signaling.


Assuntos
Quinase 3 da Glicogênio Sintase , beta Catenina , Animais , Caveolina 1/genética , Caveolina 1/metabolismo , Caveolina 1/farmacologia , Diferenciação Celular , Quinase 3 da Glicogênio Sintase/metabolismo , Quinase 3 da Glicogênio Sintase/farmacologia , Camundongos , Desenvolvimento Muscular/genética , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo
19.
Nat Commun ; 13(1): 1642, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35347134

RESUMO

Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous cancer with limited understanding of its classification and tumor microenvironment. Here, by performing single-cell RNA sequencing on 144,878 cells from 14 pairs of iCCA tumors and non-tumor liver tissues, we find that S100P and SPP1 are two markers for iCCA perihilar large duct type (iCCAphl) and peripheral small duct type (iCCApps). S100P + SPP1- iCCAphl has significantly reduced levels of infiltrating CD4+ T cells, CD56+ NK cells, and increased CCL18+ macrophages and PD1+CD8+ T cells compared to S100P-SPP1 + iCCApps. The transcription factor CREB3L1 is identified to regulate the S100P expression and promote tumor cell invasion. S100P-SPP1 + iCCApps has significantly more SPP1+ macrophage infiltration, less aggressiveness and better survival than S100P + SPP1- iCCAphl. Moreover, S100P-SPP1 + iCCApps harbors tumor cells at different status of differentiation, such as ALB + hepatocyte differentiation and ID3+ stemness. Our study extends the understanding of the diversity of tumor cells in iCCA.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , Linfócitos T CD8-Positivos/metabolismo , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Humanos , Transcriptoma , Microambiente Tumoral/genética
20.
Phytochemistry ; 198: 113155, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35259348

RESUMO

Cynomorium coccineum subsp. songaricum (Rupr.) J. Leonard has been widely used as a Chinese herbal remedy or a functional food for treating symptoms of aging or neurodegenerative diseases. A further investigation on the finding of active constituents led to the isolation and identification of four previously undescribed triterpenoids, together with 20 known compounds. Their structures were elucidated by extensive spectroscopic analysis (IR, NMR, HRMS, and CD). Sixteen compounds showed significant neuroprotective effects against glutamate-induced or oxygen-glucose deprivation-induced SK-N-SH cell death. Our findings revealed the active constituents of C. coccineum subsp. songaricum and indicated that both oleanane-type and ursane-type triterpenes could be valuable platforms for neurodegenerative agents based on primary structure-activity relationship analysis.


Assuntos
Cynomorium , Medicamentos de Ervas Chinesas , Fármacos Neuroprotetores , Triterpenos , Cynomorium/química , Medicamentos de Ervas Chinesas/química , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Triterpenos/farmacologia
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