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1.
EMBO J ; 42(21): e113448, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37737560

RESUMO

The nucleosome remodeling and histone deacetylase (NuRD) complex physically associates with BCL11B to regulate murine T-cell development. However, the function of NuRD complex in mature T cells remains unclear. Here, we characterize the fate and metabolism of human T cells in which key subunits of the NuRD complex or BCL11B are ablated. BCL11B and the NuRD complex bind to each other and repress natural killer (NK)-cell fate in T cells. In addition, T cells upregulate the NK cell-associated receptors and transcription factors, lyse NK-cell targets, and are reprogrammed into NK-like cells (ITNKs) upon deletion of MTA2, MBD2, CHD4, or BCL11B. ITNKs increase OPA1 expression and exhibit characteristically elongated mitochondria with augmented oxidative phosphorylation (OXPHOS) activity. OPA1-mediated elevated OXPHOS enhances cellular acetyl-CoA levels, thereby promoting the reprogramming efficiency and antitumor effects of ITNKs via regulating H3K27 acetylation at specific targets. In conclusion, our findings demonstrate that the NuRD complex and BCL11B cooperatively maintain T-cell fate directly by repressing NK cell-associated transcription and indirectly through a metabolic-epigenetic axis, providing strategies to improve the reprogramming efficiency and antitumor effects of ITNKs.


Assuntos
Histonas , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase , Animais , Humanos , Camundongos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/genética , Dinâmica Mitocondrial , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Linfócitos T/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo
2.
BMC Genomics ; 25(1): 227, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429743

RESUMO

BACKGROUND: Hybridization capture-based targeted next generation sequencing (NGS) is gaining importance in routine cancer clinical practice. DNA library preparation is a fundamental step to produce high-quality sequencing data. Numerous unexpected, low variant allele frequency calls were observed in libraries using sonication fragmentation and enzymatic fragmentation. In this study, we investigated the characteristics of the artifact reads induced by sonication and enzymatic fragmentation. We also developed a bioinformatic algorithm to filter these sequencing errors. RESULTS: We used pairwise comparisons of somatic single nucleotide variants (SNVs) and insertions and deletions (indels) of the same tumor DNA samples prepared using both ultrasonic and enzymatic fragmentation protocols. Our analysis revealed that the number of artifact variants was significantly greater in the samples generated using enzymatic fragmentation than using sonication. Most of the artifacts derived from the sonication-treated libraries were chimeric artifact reads containing both cis- and trans-inverted repeat sequences of the genomic DNA. In contrast, chimeric artifact reads of endonuclease-treated libraries contained palindromic sequences with mismatched bases. Based on these distinctive features, we proposed a mechanistic hypothesis model, PDSM (pairing of partial single strands derived from a similar molecule), by which these sequencing errors derive from ultrasonication and enzymatic fragmentation library preparation. We developed a bioinformatic algorithm to generate a custom mutation "blacklist" in the BED region to reduce errors in downstream analyses. CONCLUSIONS: We first proposed a mechanistic hypothesis model (PDSM) of sequencing errors caused by specific structures of inverted repeat sequences and palindromic sequences in the natural genome. This new hypothesis predicts the existence of chimeric reads that could not be explained by previous models, and provides a new direction for further improving NGS analysis accuracy. A bioinformatic algorithm, ArtifactsFinder, was developed and used to reduce the sequencing errors in libraries produced using sonication and enzymatic fragmentation.


Assuntos
Artefatos , Genoma Humano , Humanos , Biblioteca Gênica , Análise de Sequência de DNA/métodos , DNA de Neoplasias , Sequenciamento de Nucleotídeos em Larga Escala/métodos
3.
Plant Physiol ; 192(2): 1115-1131, 2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-36943300

RESUMO

Stem cells are the ultimate source of cells for various tissues and organs and thus are essential for postembryonic plant growth and development. SCARECROW (SCR) is a plant-specific transcription regulator well known for its role in stem cell renewal in plant roots, but the mechanism by which SCR exerts this function remains unclear. To address this question, we carried out a genetic screen for mutants that no longer express SCR in the stem cell niche of Arabidopsis (Arabidopsis thaliana) roots and characterized 1 of these mutants. Molecular genetics methods allowed us to pinpoint the causal mutation in this mutant in TELOMERIC PATHWAYS IN ASSOCIATION WITH STN 1 (TEN1), encoding a factor that protects telomere ends. Interestingly, TEN1 expression was dramatically reduced in the scr mutant. Telomerase and STN1 and CONSERVED TELOMERE MAINTENANCE COMPONENT 1 (CTC1), components of the same protein complex as TEN1, were also dramatically downregulated in scr. Loss of STN1, CTC1, and telomerase caused defects in root stem cells. These results together suggest that SCR maintains root stem cells by promoting expression of genes that ensure genome integrity. Supporting this conclusion, we demonstrated that the scr mutant accumulates more DNA damage than wild-type Arabidopsis and that this problem is aggravated after exposure to zeocin, a DNA damage reagent. Finally, we identified 2 previously uncharacterized motifs in TEN1 and provide evidence that a conserved amino acid residue in 1 of the motifs is indispensable for TEN1 function. SCR thus provides a connection between genome integrity and stem cell maintenance in Arabidopsis roots.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Telomerase , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Nicho de Células-Tronco/genética , Telomerase/genética , Telomerase/metabolismo , Telômero/genética , Telômero/metabolismo
4.
FASEB J ; 37(3): e22782, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36786721

RESUMO

Ischemia-reperfusion (I/R) injury is a crucial factor causing liver injury in the clinic. Recent research has confirmed that human adipose-derived stem cells (ADSCs) can differentiate into functional hepatocytes. However, the mechanism of the effects of ADSCs in the treatment of liver injury remains unclear. The characteristics of ADSCs were first identified, and exosome-derived ADSCs were isolated and characterized. The function and mechanism of action of miR-183 and arachidonate 5-lipoxygenase (ALOX5) were investigated by functional experiments in HL-7702 cells with I/R injury and in I/R rats. Our data disclosed that exosome release from ADSCs induced proliferation and inhibited apoptosis in HL-7702 cells with I/R injury. The effect of miR-183 was similar to that of exosomes derived from ADSCs. In addition, ALOX5, as a target gene of miR-183, was involved in the related functions of miR-183. Moreover, in vivo experiments confirmed that miR-183 and exosomes from ADSCs could improve liver injury in rats and inhibit the MAPK and NF-κB pathways. All of these findings demonstrate that exosomes derived from ADSCs have a significant protective effect on hepatic I/R injury by regulating the miR-183/ALOX5 axis, which might provide a therapeutic strategy for liver injury.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Traumatismo por Reperfusão , Humanos , Ratos , Animais , Linhagem Celular , MicroRNAs/genética , MicroRNAs/metabolismo , Exossomos/metabolismo , Araquidonato 5-Lipoxigenase/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fígado/metabolismo , Reperfusão , Traumatismo por Reperfusão/metabolismo
5.
Acta Biochim Biophys Sin (Shanghai) ; 56(6): 833-843, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38716542

RESUMO

Acute rejection is an important factor affecting the survival of recipients after liver transplantation. Salidroside has various properties, including anti-inflammatory, antioxidant, and hepatoprotective properties. This study aims to investigate whether salidroside can prevent acute rejection after liver transplantation and to examine the underlying mechanisms involved. An in vivo acute rejection model is established in rats that are pretreated with tacrolimus (1 mg/kg/d) or salidroside (10 or 20 mg/kg/d) for seven days after liver transplantation. In addition, an in vitro experiment is performed using neutrophils incubated with salidroside (1, 10, 50 or 100 µM). Hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, immunosorbent assays, immunofluorescence analysis, Evans blue staining, and western blot analysis are performed to examine the impact of salidroside on NET formation and acute rejection in vitro and in vivo. We find that Salidroside treatment reduces pathological liver damage, serum aminotransferase level, and serum levels of IL-1ß, IL-6, and TNF-α in vivo. The expressions of proteins associated with the HMGB1/TLR-4/MAPK signaling pathway (HMGB1, TLR-4, p-ERK1/2, p-JNK, p-P38, cleaved caspase-3, cleaved caspase-9, Bcl-2, Bax, IL-1ß, TNF-α, and IL-6) are also decreased after salidroside treatment. In vitro experiments show that the release of HMGB1/TLR-4/MAPK signaling pathway-associated proteins from neutrophils treated with lipopolysaccharide is decreased by salidroside. Moreover, salidroside inhibits NETosis and protects against acute rejection by regulating the HMGB1/TLR-4/MAPK signaling pathway. Furthermore, salidroside combined with tacrolimus has a better effect than either of the other treatments alone. In summary, salidroside can prevent acute liver rejection after liver transplantation by reducing neutrophil extracellular trap development through the HMGB1/TLR-4/MAPK signaling pathway.


Assuntos
Armadilhas Extracelulares , Glucosídeos , Rejeição de Enxerto , Proteína HMGB1 , Transplante de Fígado , Neutrófilos , Fenóis , Receptor 4 Toll-Like , Animais , Fenóis/farmacologia , Glucosídeos/farmacologia , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/metabolismo , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/patologia , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/metabolismo , Proteína HMGB1/metabolismo , Receptor 4 Toll-Like/metabolismo , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Ratos , Ratos Sprague-Dawley , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Apoptose/efeitos dos fármacos
6.
Angew Chem Int Ed Engl ; 63(8): e202315362, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38117012

RESUMO

In current approaches for circularly polarized phosphorescent materials, the crystallization of chiral phosphors suffers from poor processability, while integrating them into an amorphous polymer matrix results in unsatisfactory chiroptical signals due to the absence of chirality communication. Here, we have developed an innovative strategy through chiral supramolecular polymerization of benzil phosphors facilitated by intermolecular hydrogen bonds. The inherent film-forming capabilities of non-covalent supramolecular polymers obviate the need for an external polymer matrix. The pronounced helical asymmetry of benzil phosphors resulting from chiral supramolecular polymerization leads to enhanced circularly polarized phosphorescence compared to their non-hydrogen-bonded counterparts. The circularly polarized phosphorescent signals can be further modulated by varying the location of stereogenic centers or introducing halogen bonding to benzils. Incorporation of platinum(II) phosphor into the benzil supramolecular polymers induces both chirality and triplet-to-triplet energy transfer, leading to a change in circularly polarized phosphorescent color from yellow to red. In summary, chiral supramolecular polymerization of phosphors represents a novel and effective approach to circularly polarized phosphorescent materials.

7.
J Chem Phys ; 158(8): 084702, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36859079

RESUMO

Out-of-plane deformation in graphene is unavoidable during both synthesis and transfer procedures due to its special flexibility, which distorts the lattice and eventually imposes crucial effects on the physical features of graphene. Nowadays, however, little is known about this phenomenon, especially for zero-dimensional bulges formed in graphene. In this work, employing first-principles-based theoretical calculations, we systematically studied the bulge effect on the geometric, electronic, and transport properties of graphene. We demonstrate that the bulge formation can introduce mechanical strains (lower than 2%) to the graphene's lattice, which leads to a significant charge redistribution throughout the structure. More interestingly, a visible energy band splitting was observed with the occurrence of zero-dimensional bulges in graphene, which can be attributed to the interlayer coupling that stems from the bulged structure. In addition, it finds that the formed bulges in graphene increase the electron states near the Fermi level, which may account for the enhanced carrier concentration. However, the lowered carrier mobility and growing phonon scattering caused by the formed bulges diminish the transport of both electrons and heat in graphene. Finally, we indicate that bulges arising in graphene increase the possibility of intrinsic defect formation. Our work will evoke attention to the out-of-plane deformation in 2D materials and provide new light to tune their physical properties in the future.

8.
World J Microbiol Biotechnol ; 39(7): 170, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37185920

RESUMO

The lichen-forming fungus Umbilicaria muehlenbergii undergoes a phenotypic transition from a yeast-like to a pseudohyphal form. However, it remains unknown if a common mechanism is involved in the phenotypic switch of U. muehlenbergii at the transcriptional level. Further, investigation of the phenotype switch molecular mechanism in U. muehlenbergii has been hindered by incomplete genomic sequencing data. Here, the phenotypic characteristics of U. muehlenbergii were investigated after cultivation on several carbon sources, revealing that oligotrophic conditions due to nutrient stress (reduced strength PDA (potato dextrose agar) media) exacerbated the pseudohyphal growth of U. muehlenbergii. Further, the addition of sorbitol, ribitol, and mannitol exacerbated the pseudohyphal growth of U. muehlenbergii regardless of PDA medium strength. Transcriptome analysis of U. muehlenbergii grown in normal and nutrient-stress conditions revealed the presence of several biological pathways with altered expression levels during nutrient stress and related to carbohydrate, protein, DNA/RNA and lipid metabolism. Further, the results demonstrated that altered biological pathways can cooperate during pseudohyphal growth, including pathways involved in the production of protectants, acquisition of other carbon sources, or adjustment of energy metabolism. Synergistic changes in the functioning of these pathways likely help U. muehlenbergii cope with dynamic stimuli. These results provide insights into the transcriptional response of U. muehlenbergii during pseudohyphal growth under oligotrophic conditions. Specifically, the transcriptomic analysis indicated that pseudohyphal growth is an adaptive mechanism of U. muehlenbergii that facilitates its use of alternative carbon sources to maintain survival.


Assuntos
Ascomicetos , Ascomicetos/genética , Saccharomyces cerevisiae/genética , Fenótipo , Carbono
9.
Angew Chem Int Ed Engl ; 62(36): e202305827, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37431813

RESUMO

Controlling the nanoscale orientation of π-conjugated systems remains challenging due to the complexity of multiple energy landscapes involved in the supramolecular assembly process. In this study, we have developed an effective strategy for programming the pathways of π-conjugated supramolecular polymers, by incorporating both electron-rich methoxy- or methanthiol-benzene as donor unit and electron-poor cyano-vinylenes as acceptor units on the monomeric structure. It leads to the formation of parallel-stacked supramolecular polymers as the metastable species through homomeric donor/acceptor packing, which convert to slip-stacked supramolecular polymers as the thermodynamically stable species facilitated by heteromeric donor-acceptor packing. By further investigating the external seed-induced kinetic-to-thermodynamic transformation behaviors, our findings suggest that the donor-acceptor functionality on the seed structure is crucial for accelerating pathway conversion. This is achieved by eliminating the initial lag phase in the supramolecular polymerization process. Overall, this study provides valuable insights into designing molecular structures that control aggregation pathways of π-conjugated nanostructures.

10.
J Am Chem Soc ; 144(22): 9775-9784, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35621014

RESUMO

Chirality delivers substantial value to the field of supramolecular polymers, not only serving as a probe to monitor the dynamic assembly process but providing access to chiroptical materials. The current study demonstrates that, for supramolecular donor-acceptor copolymers, their comonomer organization modes can be greatly influenced by stereocommunication at the molecular level. The enantiopure N-[(1R or 1S)-phenylethyl]benzamides are incorporated into two structurally similar comonomers, locating between the π-aromatic diethynylacene core and the alkyl chain peripheries. Parallel arrangement of the stereogenic methyl units brings steric hindrance between the homochiral comonomers, which is relieved for the heterochiral comonomers due to the adoption of staggered arrangement. It consequently steers randomly mixed organization for the homochiral supramolecular copolymers within the nanofibers. In comparison, the heterochiral counterparts form nanoparticles in an alternate donor-acceptor organization manner. The variation of comonomer arrangement modes gives rise to distinct energy transfer efficiency at the supramolecular level. Overall, the elaborate manipulation of stereogenic centers in the comonomer structures exerts significant impacts on the characteristics of supramolecular copolymers, which could be useful for chiral sensing, recognition, and optoelectronic applications.

11.
Plant Physiol ; 187(1): 303-320, 2021 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-34618128

RESUMO

The energy allocation for vegetative and reproductive growth is regulated by developmental signals and environmental cues, which subsequently affects seed output. However, the molecular mechanism underlying how plants coordinate yield-related traits to control yield in changing source-sink relationships remains largely unknown. Here, we discovered the lectin receptor-like kinase LecRK-VIII.2 as a specific receptor-like kinase that coordinates silique number, seed size, and seed number to determine seed yield in Arabidopsis (Arabidopsis thaliana). The lecrk-VIII.2 mutants develop smaller seeds, but more siliques and seeds, leading to increased yield. In contrast, the plants overexpressing LecRK-VIII.2 form bigger seeds, but less siliques and seeds, which results in similar yield to that of wild-type plants. Interestingly, LecRK-VIII.2 promotes the growth of the rosette, root, and stem by coordinating the source-sink relationship. Additionally, LecRK-VIII.2 positively regulates cell expansion and proliferation in the seed coat, and maternally controls seed size. The genetic and biochemical analyses demonstrated that LecRK-VIII.2 acts upstream of the mitogen-activated protein kinase (MAPK) gene MPK6 to regulate silique number, seed size, and seed number. Collectively, these findings uncover LecRK-VIII.2 as an upstream component of the MAPK signaling pathway to control yield-related traits and suggest its potential for crop improvement aimed at developing plants with stable yield, a robust root system, and improved lodging resistance.


Assuntos
Arabidopsis , Proteínas Quinases Ativadas por Mitógeno , Transdução de Sinais , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas Quinases Ativadas por Mitógeno/genética
12.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(6): 1033-1039, 2022 Dec.
Artigo em Zh | MEDLINE | ID: mdl-36621794

RESUMO

Objective To investigate the expression of androgen receptor(AR)and its correlations with different molecular subtypes and clinicopathological features of breast invasive carcinoma of no special type(IBC-NST)in females of Tibetan ethnic minority in Tibet.Methods This study enrolled 54 female patients of Tibetan ethnic minority with IBC-NST surgically removed in the Tibet Autonomous Region People's Hospital from December 2015 to March 2021 for retrospective analysis.The clinical and pathological data of all the enrolled patients were collected.The immunohistochemical method was employed to determine the expression of AR,cell proliferation marker antigen (Ki-67),estrogen receptor(ER),human epidermal growth factor receptor 2(HER-2),and progesterone receptor(PR).For those with unclear HER-2 results,fluorescence in situ hybridization was employed for the determination.The relationship of AR expression with molecular subtypes and clinicopathological features was then analyzed.Results The expression of AR in Tibetan female patients with IBC-NST was correlated with ER(χ2=8.200,P=0.004),PR(χ2=9.900,P=0.003),and molecular subtype(χ2=11.690,P=0.009)and not correlated with tumor location,age,size,histological grade,lymph node metastasis,vascular invasion,clinical stage,or expression of HER-2 and Ki-67(all P>0.05).Molecular subtype was correlated with histological grade(χ2=24.970, P=0.001),clinical stage(χ2=9.035, P=0.029),and lymph node metastasis(χ2=9.691,P=0.021).Conclusions The positive expression rate of AR in the triple-negative IBC-NST patients of Tibetan ethnic minority was significantly lower than that in ER-or PR-positive patients in Tibet.Molecular subtype was correlated with histological grade,clinical stage,and lymph node metastasis.


Assuntos
Neoplasias da Mama , Receptores Androgênicos , Humanos , Feminino , Tibet , Metástase Linfática , Antígeno Ki-67 , Receptores Androgênicos/metabolismo , Estudos Retrospectivos , Androgênios , Hibridização in Situ Fluorescente , Etnicidade , Grupos Minoritários , Neoplasias da Mama/metabolismo , Receptor ErbB-2 , Receptores de Estrogênio , Receptores de Progesterona
13.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(4): 621-627, 2022 Aug.
Artigo em Zh | MEDLINE | ID: mdl-36065695

RESUMO

Objective To analyze the clinicopathological features and immunohistochemical expression of meningiomas in the Tibetan population in Tibet,and improve the understanding of meningiomas. Methods The clinical and pathological data of all the meningiomas diagnosed by pathology in Tibet Autonomous Region People's Hospital from April 2013 to March 2021 were analyzed retrospectively.All the cases underwent immunohistochemical staining of trimethylation of lysine 27 on histone H3 (H3K27me3),mucin 4 (MUC4),somatostatin receptor 2 (SSTR2),progesterone receptor,epithelial membrane antigen,glial fibrillary acidic protein,vimentin,S-100,P53,and Ki-67.The histopathological features and the staining results were observed under a light microscope. Results A total of 116 cases of meningiomas were included in this study,with the male-to-female ratio of 1.0∶2.6 and the age of 4-73 years.The main clinical symptom was headache.The imaging examination showed that 114 cases had single lesions and 2 cases had multiple lesions.The tumors were located in the cranium (108 cases) and spinal canal (8 cases).The maximum diameter of the tumors ranged from 0.3 cm to 10.0 cm,with a mean of (5.7±2.2) cm.In terms of microscopic grading and histological types,the 116 cases included 111 cases of WHO grade Ⅰ (including 53 cases of fibrous type,20 cases of meningothelial type,24 cases of transitional type,10 cases of psammomatous type,etc.),4 cases of WHO grade Ⅱ (3 cases of atypical type and 1 case of clear cell type),and 1 case of WHO grade Ⅲ (papillary type).The immunohistochemical staining showed H3K27me3 expression absent in 9 cases (9/116,7.8%),MUC4 positive in 64 cases (64/116,55.2%),SSTR2 positive in 101 cases (101/116,87.1%).Eighty cases had follow-up results,among which 71 cases had no recurrence,while 9 cases recurred. Conclusions Meningioma is the most common tumor in the central nervous system in the pathological file of Tibet.It mainly attacks the middle-aged female patients,occupying the parasagittal sinus,falx,and convex surface of the brain.Fibrous meningioma of WHO grade Ⅰ is common,while the meningiomas of WHO grades Ⅱ and Ⅲ are rare.The expression degree of MUC4 is higher in meningothelial and transitional meningiomas but lower in fibrous meningiomas.There may be no correlation between the absence of H3K27me3 expression and prognosis.


Assuntos
Neoplasias Meníngeas , Meningioma , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Histonas , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Tibet , Adulto Jovem
14.
Lab Invest ; 101(5): 570-587, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33772101

RESUMO

Hepatocellular carcinoma (HCC) is a rapidly growing tumor characterized by a high potential for vascular invasion and metastasis. The purpose of our study is to explore the regulation mechanism of long noncoding RNA (lncRNA) LINC01419 on cell-cycle distribution and metastasis in hepatocellular carcinoma (HCC) by regulating zinc finger of the cerebellum (ZIC1) through PI3K/Akt signaling pathway. Bioinformatics analysis and dual-luciferase reporter assay were used to analyze LINC01419 and related genes in HCC, and their expression in HCC tissues and adjacent normal tissues were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. Then, HCC cell lines were subjected to the construction of LINC01419/ZIC1 overexpression/knockdown cells utilizing lentiviral vectors. RIP and ChIP assays were applied to identify the LINC01419-binding protein. BSP and MSP assays were used to determine gene methylation. According to the results, LINC01419 was highly expressed in HCC tissues and cells, while ZIC1 was poorly expressed. LINC01419 targeted and downregulated ZIC1 expression. Furthermore, LINC01419 increased the methylation of ZIC1 promoter and repressed ZIC1 expression. PI3K/Akt signaling pathway was activated by LINC01419 overexpression and ZIC1 knockdown, under which conditions, the HCC cell self-renewal and proliferation were promoted while cell apoptosis was attenuated, accompanied by accelerated formation and metastasis of xenografted tumors in mice. In conclusion, LINC01419 enhances the methylation of ZIC1 promoter, inhibits ZIC1 expression, and activates the PI3K/Akt signaling pathway, thereby enhancing the malignant phenotypes of HCC cells in vitro as well as tumor formation and metastasis in vivo.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Linhagem Celular Tumoral , Metilação de DNA , Progressão da Doença , Epigênese Genética , Feminino , Inativação Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição/genética , Adulto Jovem
15.
BMC Cancer ; 21(1): 259, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33691643

RESUMO

BACKGROUND: The incidence and mortality of lung cancer are the highest among all cancers. Patients with systemic sclerosis show a four-fold greater risk of lung cancer than the general population. However, the underlying mechanism remains poorly understood. METHODS: The expression profiles of 355 peripheral blood samples were integratedly analyzed, including 70 cases of lung cancer, 61 cases of systemic sclerosis, and 224 healthy controls. After data normalization and cleaning, differentially expressed genes (DEGs) between disease and control were obtained and deeply analyzed by bioinformatics methods. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed online by DAVID and KOBAS. The protein-protein interaction (PPI) networks were constructed from the STRING database. RESULTS: From a total of 14,191 human genes, 299 and 1644 genes were identified as DEGs in systemic sclerosis and lung cancer, respectively. Among them, 64 DEGs were overlapping, including 36 co-upregulated, 10 co-downregulated, and 18 counter-regulated DEGs. Functional and enrichment analysis showed that the two diseases had common changes in immune-related genes. The expression of innate immune response and response to virus-related genes increased significantly, while the expression of negative regulation of cell cycle-related genes decreased notably. In contrast, the expression of mitophagy regulation, chromatin binding and fatty acid metabolism-related genes showed distinct trends. CONCLUSIONS: Stable differences and similarities between systemic sclerosis and lung cancer were revealed. In peripheral blood, enhanced innate immunity and weakened negative regulation of cell cycle may be the common mechanisms of the two diseases, which may be associated with the high risk of lung cancer in systemic sclerosis patients. On the other hand, the counter-regulated DEGs can be used as novelbiomarkers of pulmonary diseases. In addition, fat metabolism-related DEGs were consideredto be associated with clinical blood lipid data.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Redes Reguladoras de Genes , Neoplasias Pulmonares/genética , Escleroderma Sistêmico/genética , Estudos de Casos e Controles , Biologia Computacional , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Voluntários Saudáveis , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/imunologia , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genética , Fatores de Risco , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/imunologia
16.
BMC Public Health ; 21(1): 136, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446168

RESUMO

BACKGROUND: Racial and ethnic disparities in stillbirth risk had been documented in most western countries, but it remains unknown in China. This study was to determine whether exist ethnic disparities in stillbirth risk in mainland China. METHODS: Pregnancy outcomes and ethnicity data were obtained from the National Free Preconception Health Examination Project (NEPHEP), a nationwide prospective population-based cohort study conducted in Yunnan China from 2010-2018. The Han majority and other four main minorities including Yi, Dai, Miao, Hani were investigated in the analysis. The stillbirth hazards were estimated by life-table analysis. The excess stillbirth risk (ESR) was computed for Chinese minorities using multivariable logistic regression. RESULTS: Compared with other four minorities, women in Han majority were more likely to more educated, less multiparous, and less occupied in agriculture. The pattern of stillbirth hazard of Dai women across different gestation intervals were found to be different from other ethnic groups, especially in 20-23 weeks with 3.2 times higher than Han women. The ESR of the Dai, Hani, Miao, and Yi were 45.05, 18.70, -4.17 and 12.28%, respectively. Adjusted for maternal age, education, birth order and other general risk factors, the ethnic disparity still persisted between Dai women and Han women. Adjusted for preterm birth further (gestation age <37 weeks) can reduce 16.91% ESR of Dai women and made the disparity insignificant. Maternal diseases and congenital anomalies explained little for ethnic disparities. CONCLUSIONS: We identified the ethnic disparity in stillbirth risk between Dai women and Han women. General risk factors including sociodemographic factors and maternal diseases explained little. Considerable ethnic disparities can be attributed to preterm birth.


Assuntos
Etnicidade , Nascimento Prematuro , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Estudos Prospectivos , Natimorto/epidemiologia
17.
BMC Public Health ; 21(1): 2095, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34781900

RESUMO

BACKGROUND: China is facing big challenges to achieve the "90-90-90 targets". The HIV prevalence of elderly (≥50 years) men have been steadily increasing in China, mainly through the sexual transmission route, but sexual behaviors of them are far from well-studied. In 2019, elderly men accounted for 59.2% of HIV/AIDS cases in Sichuan, China. METHODS: The research design is a cross-sectional study. Face-to-face interviews were conducted among 795 HIV negative elderly men from rural Chengdu, capital City of Sichuan. Bivariate and multivariate logistic regression models were applied to examine factors associated with commercial heterosexual behavior from a modified Knowledge-Attitude-Practice (KAP) perspective. RESULTS: 129 (16.23%) respondents admitted high-risk sexual behaviors, including 11.07% commercial heterosexual behavior, 6.16% extramarital, 2.89% casual and 0.25% homosexual behavior, and no one used condom consistently. 427(68.43%) had ever gotten HIV-related Health Education (HRHE), mainly through mass media (70.49%). The HIV-related knowledge awareness rate was only 31.41%. Migration history (AOR =2.46,95% CI = 1.02-5.91), age(≥60 vs. 50-59, OR = 0.41, 95% CI = 0.19-0.91), receiving HRHE from mass media (OR = 0.37, 95%CI = 0.16-0.85), marital status (married vs. never married, OR = 0.04, 95%CI = 0-0.52), and undecided (AOR =0.02, 95%CI = 0.01-0.09) and objection (AOR =0.04, 95%CI = 0.01-0.1) attitude toward commercial sex were related to lifetime commercial heterosexual behavior. CONCLUSIONS: High-risk sexual behaviors are common among elderly men from rural areas in Chengdu. Receiving HRHE from mass media and undecided and objection attitude toward commercial sex prevent elderly from being involving in commercial heterosexual behavior. According to the results, health facilities should continue to conduct systematic interventions, paying more attention to 50-59 years old group. Sex and condom use need to be talked in public. Working with mass media, health facilities give elderly men education not only focusing on HIV/AIDS, but also on knowledge and skills of condom use.


Assuntos
Infecções por HIV , Heterossexualidade , Idoso , China/epidemiologia , Preservativos , Estudos Transversais , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Humanos , Masculino , Trabalho Sexual , Comportamento Sexual
18.
J Oral Maxillofac Surg ; 79(4): 748-755.e1, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33434519

RESUMO

PURPOSE: The purpose of this study was to introduce the method and first results of a modified tooth sectioning technique for the extraction of horizontally impacted mandibular third molars (M3Ms) with large root bifurcation. PATIENTS AND METHODS: A total of 300 horizontally impacted M3Ms with large root bifurcation in medically healthy patients were included in this prospective study. Patients were divided into 2 groups: the modified method group (test group), in which the M3M was sectioned between the distal root and the remainder of the tooth at the point of root bifurcation; and the conventional method group (control group), in which the M3M was sectioned between the crown and the root at the cementoenamel junction. Operation duration, postoperative reactions, complications, and patient satisfaction were analyzed and compared between the 2 groups. RESULTS: Each group included 150 M3Ms which were all successfully extracted. Operation durations in the test and control group were 10.48 ± 3.78 and 15.09 ± 4.24 minutes, respectively (P < .05). The test group had significantly better results than the control group with regard to postoperative reactions and complications (P < .05). Patients in the test group had higher satisfaction ratings regarding operation duration and the healing process than those in the control group (P < .05). CONCLUSIONS: The modified method of tooth sectioning between the distal root and the remainder of the tooth can efficiently eliminate resistance from the bone and adjacent mandibular second molar and allow for just 1 sectioning of the M3M in most cases, which could make the operation straightforward and safe.


Assuntos
Dente Serotino , Dente Impactado , Humanos , Mandíbula/cirurgia , Dente Molar , Dente Serotino/cirurgia , Estudos Prospectivos , Extração Dentária , Raiz Dentária/cirurgia , Dente Impactado/cirurgia
19.
Molecules ; 26(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068830

RESUMO

Cooperative supramolecular polymerization of π-conjugated compounds into one-dimensional nanostructures has received tremendous attentions in recent years. It is commonly achieved by incorporating amide linkages into the monomeric structures, which provide hydrogen bonds for intermolecular non-covalent complexation. Herein, the effect of amide linkages is elaborately studied, by comparing supramolecular polymerization behaviors of two structurally similar monomers with the same platinum(II) acetylide cores. As compared to the N-phenyl benzamide linkages, N-[(1S)-1-phenylethyl] benzamide linkages give rise to effective chirality transfer behaviors due to the closer distances between the chiral units and the platinum(II) acetylide core. They also provide stronger intermolecular hydrogen bonding strength, which consequently brings higher thermo-stability and enhanced gelation capability for the resulting supramolecular polymers. Supramolecular polymerization is further strengthened by varying the monomers from monotopic to ditopic structures. Hence, with the judicious modulation of structural parameters, the current study opens up new avenues for the rational design of supramolecular polymeric systems.

20.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(6): 869-874, 2021 Dec 30.
Artigo em Zh | MEDLINE | ID: mdl-34980324

RESUMO

Objective To investigate the clinicopathological features and immunohistochemical phenotypes of brain metastatic carcinoma in Tibetan patients. Methods The clinical and pathological data of all patients with brain metastases from 2014 to 2020 in Tibet Autonomous Region People's Hospital were retrospectively analyzed,including 13 cases of brain metastatic carcinoma.All cases were diagnosed and classified by immunohistochemical staining. Results 13 cases(9 males and 4 females)of brain metastatic carcinoma,aged 26-62 years old,present with headache,dizziness,nausea and vomiting clinically.Four patients had a medical history of tumor,and among the 9 patients with no history of tumor,7 present space occupying lesions in both the brain and other organs.Imaging data could be found in 10 cases,including 4 cases of single lesion and 6 cases of multiple lesions.Primary tumors were identified in 11 cases(8 located in the lung,including 4 cases of adenocarcinoma,3 cases of small cell carcinoma,and 1 case of squamous cell carcinoma;1 case of urothelial carcinoma of the renal pelvis;1 case of thyroid papillary carcinoma;1 case of uterine choriocarcinoma),whereas the primary tumor was unknown for the other 2 cases(1 case of small cell carcinoma and 1 case of adenocarcinoma). Conclusions Brain metastatic carcinoma are more common among middle-aged and elderly people in Tibet.Most of the cases have no history of tumor,with the initial site at the brain metastatic lesions.The most common primary site is the lung,and the primary site of some cases is unknown.Multiple lesions are common in brain metastatic carcinoma,especially in the cerebral hemisphere.For older patients with multiple brain space occupying lesions,the possibility of brain metastatic carcinoma increases.


Assuntos
Neoplasias Encefálicas , Carcinoma de Células de Transição , Neoplasias da Glândula Tireoide , Neoplasias da Bexiga Urinária , Adulto , Idoso , Encéfalo , Neoplasias Encefálicas/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tibet
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