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1.
Acta Pharmacol Sin ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589688

RESUMO

Lymphocyte activation gene 3 (LAG3), an immune checkpoint molecule expressed on activated T cells, functions as a negative regulator of immune responses. Persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression on T cells, contributing to T cell dysfunction. Fibrinogen-like protein 1 (FGL1) has been identified as a major ligand of LAG3, and FGL1/LAG3 interaction forms a novel immune checkpoint pathway that results in tumor immune evasion. In addition, ubiquitin-specific peptidase 7 (USP7) plays a crucial role in cancer development. In this study we investigated the role of USP7 in modulation of FGL1-mediated liver cancer immune evasion. We showed that knockdown of USP7 or treatment with USP7 inhibitor P5091 suppressed liver cancer growth by promoting CD8+ T cell activity in Hepa1-6 xenograft mice and in HepG2 or Huh7 cells co-cultured with T cells, whereas USP7 overexpression produced the opposite effect. We found that USP7 upregulated FGL1 in HepG2 and Huh7 cells by deubiquitination of transcriptional factor PR domain zinc finger protein 1 (PRDM1), which transcriptionally activated FGL1, and attenuated the CD8+ T cell activity, leading to the liver cancer growth. Interestingly, USP7 could be transcriptionally stimulated by PRDM1 as well in a positive feedback loop. P5091, an inhibitor of USP7, was able to downregulate FGL1 expression, thus enhancing CD8+ T cell activity. In an immunocompetent liver cancer mouse model, the dual blockade of USP7 and LAG3 resulted in a superior antitumor activity compared with anti-LAG3 therapy alone. We conclude that USP7 diminishes CD8+ T cell activity by a USP7/PRDM1 positive feedback loop on FGL1 production in liver cancer; USP7 might be a promising target for liver cancer immunotherapy.

2.
Nano Lett ; 23(14): 6567-6573, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37410961

RESUMO

Owing to their unique and sustainable surface plasmonic properties, Al nanocrystals have attracted increasing attention for plasmonic-enhanced applications, including single-particle surface-enhanced Raman scattering (SERS). However, whether Al nanocrystals can achieve single-particle SERS is still unknown, mainly due to the synthetic difficulty of Al nanocrystals with internal gaps. Herein, we report a regrowth method for the synthesis of Al nanohexapods with tunable and uniform internal gaps for single-particle SERS with an enhancement factor of up to 1.79 × 108. The uniform branches of the Al nanohexapods can be systematically tuned regarding their dimensions, terminated facets, and internal gaps. The Al nanohexapods generate hot spots concentrated in the internal gaps due to the strong plasmonic coupling between the branches. A single-particle SERS measurement of Al nanohexapods shows strong Raman signals with maximum enhancement factors comparable to that of Au counterparts. The large enhancement factor indicates that Al nanohexapods are good candidates for single-particle SERS.

3.
Acc Chem Res ; 55(11): 1503-1513, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35576169

RESUMO

Current interest in nanoparticle ensembles is motivated by their collective synergetic properties that are distinct from or better than those of individual nanoparticles and their bulk counterparts. These new advanced optical, electronic, magnetic, and catalytic properties can find applications in advanced nanomaterials and functional devices, if control is achieved over nanoparticle organization. Self-assembly offers a cost-efficient approach to produce ensembles of nanoparticles with well-defined and predictable structures. Nanoparticles functionalized with polymer molecules are promising building blocks for self-assembled nanostructures, due to the comparable dimensions of macromolecules and nanoparticles, the ability to synthesize polymers with various compositions, degrees of polymerization, and structures, and the ability of polymers to self-assemble in their own right. Moreover, polymer ligands can endow additional functionalities to nanoparticle assemblies, thus broadening the range of their applications.In this Account, we describe recent progress of our research groups in the development of new strategies for the self-assembly of nanoparticles tethered to macromolecules. At the beginning of our journey, we developed a new approach to patchy nanoparticles and their self-assembly. In a thermodynamically driven strategy, we used poor solvency conditions to induce homopolymer surface segregation in pinned micelles (patches). Patchy nanoparticles underwent self-assembly in a well-defined and controlled manner. Following this work, we overcame the limitation of low yield of the generation of patchy nanoparticles, by using block copolymer ligands. For block copolymer-capped nanoparticles, patch formation and self-assembly were "staged" by using distinct stimuli for each process. We expanded this work to the generation of patchy nanoparticles via dynamic exchange of block copolymer molecules between the nanoparticle surface and micelles in the solution. The scope of our work was further extended to a series of strategies that utilized the change in the configuration of block copolymer ligands during nanoparticle interactions. To this end, we explored the amphiphilicity of block copolymer-tethered nanoparticles and complementary interactions between reactive block copolymer ligands. Both approaches enabled exquisite control over directional and self-limiting self-assembly of complex hierarchical nanostructures. Next, we focused on the self-assembly of chiral nanostructures. To enable this goal, we attached chiral molecules to the surface of nanoparticles and organized these hybrid building blocks in ensembles with excellent chiroptical properties. In summary, our work enables surface engineering of polymer-capped nanoparticles and their controllable and predictable self-assembly. Future research in the field of nanoparticle self-assembly will include the development of effective characterization techniques, the synthesis of new functional polymers, and the development of environmentally responsive self-assembly of polymer-capped nanoparticles for the fabrication of nanomaterials with tailored functionalities.


Assuntos
Nanopartículas , Nanoestruturas , Ligantes , Micelas , Nanopartículas/química , Nanoestruturas/química , Polímeros/química
4.
Inorg Chem ; 62(19): 7324-7332, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37130306

RESUMO

Negative temperature coefficient (NTC) thermistors feature higher sensitivities and faster response speeds and thereby have particular applications in many fields. However, current NTC thermistors are mostly based on inorganic ceramic materials, which show obvious drawbacks in material synthesis, property modulation, and flexible film fabrication. Herein, we report, for the first time, the promising application of an inorganic-organic hybrid NTC thermistor. A new lead-free hybrid iodo bismuthate [1,1',1″-(benzene-1,3,5-triyl)tris(3-methyl-1H-imidazol-3-ium)]Bi2I9 [denoted as (Me3TMP)Bi2I9] was synthesized by a "double-free" strategy. (Me3TMP)Bi2I9 features a lead-free binuclear bismuth iodine anion charge compensated by a "classic hydrogen-bond-free" cation. (Me3TMP)Bi2I9 exhibits remarkable stability in water and UV light irradiation and shows the largest temperature sensitivity coefficient among all reported NTC materials. Theoretical calculation and detailed structural analysis disclose that the seriously distorted (BiI6) octahedra are responsible for the intriguing NTC effect for (Me3TMP)Bi2I9.

5.
Acta Pharmacol Sin ; 44(12): 2525-2536, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37474643

RESUMO

Heat shock protein family A member 8 (HSPA8) participates in the folding or degradation of misfolded proteins under stress and plays critical roles in cancer. In this study, we investigated the function of HSPA8 in the development of liver cancer. By analyzing the TCGA transcriptome dataset, we found that HSPA8 was upregulated in 134 clinical liver cancer tissue samples, and positively correlated with poor prognosis. IHC staining showed the nuclear and cytoplasmic localization of HSPA8 in liver cancer cells. Knockdown of HSPA8 resulted in a decrease in the proliferation of HepG2 and Huh-7 cells. ChIP-seq and RNA-seq analysis revealed that HSPA8 bound to the promoter of pleckstrin homology-like domain family A member 2 (PHLDA2) and regulated its expression. The transcription factor ETV4 in HepG2 cells activated PHLDA2 transcription. HSPA8 and ETV4 could interact with each other in the cells and colocalize in the nucleus. From a functional perspective, we demonstrated that HSPA8 upregulated PHDLA2 through the coactivating transcription factor ETV4 to enhance the growth of liver cancer in vitro and in vivo. From a therapeutic perspective, we identified both HSPA8 and PHDLA2 as novel targets in the treatment of HCC. In conclusion, this study demonstrates that HSPA8 serves as a coactivator of ETV4 and upregulates PHLDA2, leading to the growth of HCC, and is a potential therapeutic target in HCC treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/genética , Fatores de Transcrição/genética , Carcinoma Hepatocelular/genética , Proteínas de Choque Térmico , Regulação da Expressão Gênica , Proteínas Proto-Oncogênicas c-ets/genética
6.
Biochem Biophys Res Commun ; 594: 46-56, 2022 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-35074585

RESUMO

PURPOSE OF REVIEW: To explore the convergent downstream pathways of ketamine and rapastinel and drive further development of identification for following generational rapid-acting antidepressants in the synaptic process. RECENT FINDINGS: Ketamine is an NMDAR antagonist and is proven effective in depression for the rapid and sustained antidepressant response, while rapastinel is an NMDAR positive allosteric modulator, producing antidepressant effects like ketamine with no severe side effects. The common antidepressant effects of ketamine and rapastinel are BDNF and mTORC1 pathway in synaptic plasticity.


Assuntos
Antidepressivos/administração & dosagem , Depressão/tratamento farmacológico , Ketamina/administração & dosagem , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Oligopeptídeos/administração & dosagem , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de Neurotransmissores/metabolismo , Animais , Humanos , Camundongos , Comportamento Autodestrutivo , Transdução de Sinais , Sinapses/efeitos dos fármacos
7.
Acta Pharmacol Sin ; 43(10): 2448-2461, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35145238

RESUMO

Major depressive disorder (MDD), a chronic and recurrent disease characterized by anhedonia, pessimism or even suicidal thought, remains a major chronic mental concern worldwide. Connexin 43 (Cx43) is the most abundant connexin expressed in astrocytes and forms the gap junction channels (GJCs) between astrocytes, the most abundant and functional glial cells in the brain. Astrocytes regulate neurons' synaptic strength and function by expressing receptors and regulating various neurotransmitters. Astrocyte dysfunction causes synaptic abnormalities, which are related to various mood disorders, e.g., depression. Increasing evidence suggests a crucial role of Cx43 in the pathogenesis of depression. Depression down-regulates Cx43 expression in humans and rats, and dysfunction of Cx43 also induces depressive behaviors in rats and mice. Recently Cx43 has received considerable critical attention and is highly implicated in the onset of depression. However, the pathological mechanisms of depression-like behavior associated with Cx43 still remain ambiguous. In this review we summarize the recent progress regarding the underlying mechanisms of Cx43 in the etiology of depression-like behaviors including gliotransmission, metabolic disorders, and neuroinflammation. We also discuss the effects of antidepressants (monoamine antidepressants and ketamine) on Cx43. The clarity of the candidate pathological mechanisms of depression-like behaviors associated with Cx43 and its potential pharmacological roles for antidepressants will benefit the exploration of a novel antidepressant target.


Assuntos
Transtorno Depressivo Maior , Ketamina , Animais , Antidepressivos/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Astrócitos/metabolismo , Conexina 43/metabolismo , Conexinas/metabolismo , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Ketamina/farmacologia , Camundongos , Neurotransmissores/metabolismo , Córtex Pré-Frontal/metabolismo , Ratos
8.
Angew Chem Int Ed Engl ; 61(35): e202202405, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-35778803

RESUMO

Metal nanoparticles (NPs) stabilized with thiol- (HS-) terminated polymers have applications in medicine, optoelectronics, and catalysis. It is assumed that upon exposure to oxidants or even air, these NPs lose colloidal stability, due to the oxidation of the HS-end-group and elimination of polymer ligands from the NP surface, however, this mechanism does not explain the unsuccessful recovery of the NP stability by adding fresh HS-terminated polymers. Here we propose the oxidation of the surface metal atoms as a mechanism for the oxidative elimination of polymer from the NP surface. Based on this mechanism, we reversed NP aggregation by reducing the oxidized metal surface and re-attaching HS-terminated polymer ligands. This mechanism is general for various metal NPs and different HS-terminated polymers. We show that oxidative elimination and reductive addition reactions can improve the colloidal stability of polymer-capped metal NPs and control their redox stimuli-responsive self-assembly.


Assuntos
Nanopartículas Metálicas , Polímeros , Ouro , Ligantes , Oxirredução , Estresse Oxidativo , Compostos de Sulfidrila
9.
Eur J Neurosci ; 53(1): 140-150, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-31491043

RESUMO

The role of the fibroblast growth factor (FGF) system in depression has received considerable attention in recent years. To understand the role of this system, it is important to identify the specific members of the FGF family that have been implicated and the various mechanisms that they modulated. Here, we review the role of FGFs in depression and integrate evidence from clinical and basic research. These data suggest that changes in the FGF family are involved in depression and possibly in a wider range of psychiatric disorders. We analyse the abnormalities of FGF family members in depression and their roles in modulating depression-related molecules. The role of the FGF family in depression and related disorders needs to be studied in more detail.


Assuntos
Depressão , Transtornos Mentais , Fatores de Crescimento de Fibroblastos/genética , Humanos , Receptores de Fatores de Crescimento de Fibroblastos
10.
Soft Matter ; 17(26): 6298-6304, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34160542

RESUMO

Chiral assemblies by combining natural biomolecules with plasmonic nanostructures hold great promise for plasmonic enhanced sensing, imaging, and catalytic applications. Herein, we demonstrate that human serum albumin (HSA) and porcine serum albumin (PSA) can guide the chiral assembly of gold nanorods (GNRs) with left-handed chiroptical responses opposite to those by a series of other homologous animal serum albumins (SAs) due to the difference of their surface charge distributions. Under physiological pH conditions, the assembly of HSA or PSA with GNRs yielded left-handed twisted aggregates, while bovine serum albumin (BSA), sheep serum albumin, and equine serum albumin behaved on the contrary. The driving force for the chiral assembly is mainly attributed to electrostatic interaction. The opposite chiroptical signals acquired are correlated with the chiral surface charge distributions of the tertiary structures of SAs. Moreover, the chirality of the assembly induced by both HSA and BSA can be enhanced or reversed by adjusting the pH values. This work provides new insights into the modulation of protein-induced chiral assemblies and promotes their applications.


Assuntos
Nanoestruturas , Nanotubos , Animais , Ouro , Cavalos , Albumina Sérica , Soroalbumina Bovina , Ovinos
11.
BMC Pregnancy Childbirth ; 21(1): 815, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34879840

RESUMO

BACKGROUND: Cesarean scar defect (CSD), especially CSD with residual myometrium less than 3 mm is reported to be the highest risk agent associated with uterine rupture for subsequent pregnancy. Currently, laparoscopic resection and suture was the mainstay therapy method for CSD with a residual myometrium less than 3 mm in women with a desire to conceive. Besides, the women have CSD related symptoms, especially postmenstrual bleeding, should be recommended for CSD treatment. This study is to investigate the efficiency of this novel laparoscopic surgery for the repair of cesarean scar defect (CSD) without scar resection for residual myometrium thickening. METHOD: This retrospective clinical study enrolled 76 women diagnosed with CSD who had a residual myometrium thickness less than 3 mm and also had a desire to conceive, had undergone laparoscopic surgery for the repair of CSD in the time period March 2016 to March 2018. Two study cohorts were created among the 76 patients: 40 patients had undergone the novel laparoscopic repair of CSD without processing scar resection (Group A), whereas 36 patients had undergone the traditional laparoscopic resection and suture of CSD (Group B). RESULTS: Residual myometrium thickening occurred among all the 76 patients and the average residual myometrium thickness was increased to almost 6 mm, presenting no between-group difference. In Group A, all the CSD-related postmenstrual bleeding was resolved or improved, but one patient in Group B has no obvious change to postmenstrual bleeding. After CSD repair, 20 patients got pregnant naturally in Group A, and there was no cesarean scar pregnancy and uterine rupture. While, there were 9 cases of natural pregnancy in Group B. No uterine rupture occurred among these 9 pregnant women of Group B, but 1 case of pregnancy was terminated due to cesarean scar pregnancy. CONCLUSION: Laparoscopic repair without processing scar resection seems to be a feasible, safe and simple operative approach for CSD treatment, which can thicken residual myometrium and improve postmenstrual bleeding.


Assuntos
Cesárea/efeitos adversos , Cicatriz/etiologia , Cicatriz/reabilitação , Cicatriz/cirurgia , Laparoscopia/métodos , Estudos de Coortes , Feminino , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Miométrio/cirurgia , Gravidez , Estudos Retrospectivos , Técnicas de Sutura , Hemorragia Uterina/cirurgia
12.
Angew Chem Int Ed Engl ; 60(4): 2018-2023, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-32885573

RESUMO

A new and simple strategy towards electric-field-driven multiple chirality switching device has been designed and fabricated by combining a newly synthesized base-responsive chiroptical polymer switch (R-FLMA) and p-benzoquinone (p-BQ) via proton-coupled electron transfer (PCET) mechanism. Clear and stable triple chirality states (silence, positive, negative) of this device in visible band can be regulated reversibly (>1000 cycles) by adjusting voltage programs. Furthermore, such chiral switching phenomena are also accompanied by apparent changes of color and fluorescence. More importantly, the potential application of this device for a spatial light modulator has also been demonstrated.

13.
J Minim Invasive Gynecol ; 27(3): 582, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31374341

RESUMO

OBJECTIVE: To introduce an effective method combining various endoscopes in the treatment of intravesical migrated intrauterine device (IUD). DESIGN: A step-by-step explanation of the surgery using video, approved by the Shengjing Hospital of China Medical University. SETTING: Shengjing Hospital of China Medical University. INTERVENTIONS: A 39-year-old young woman, in whom an IUD was inserted 2 months prior, presented with frequent urination after IUD insertion. Cystoscope and pelvic computed tomography were performed, and the results showed an IUD in the bladder. The migrated IUD was found partly in the uterus and partly in the bladder by hysteroscope and cystoscope. Management of the migrated IUD consists of 4 steps: (1) lysing the adhesion between the bladder and uterus, (2) suturing the bladder and taking the IUD part out of the bladder, (3) removing the IUD part in the uterus, and (4) suturing the bladder again to reinforce it and suturing the uterus. CONCLUSION: The migrated IUD in the bladder was successfully and completely extracted by the method combining various endoscopes; operative time was 56 minutes. In the follow-up period the patient did not report any symptoms of frequency urination. This surgical process has the following characteristics: Preoperative examination should be performed to clarify the ectopic site of the IUD, various endoscopes should be combined for diagnosis and treatment, and endoscopic surgery is an effective treatment method for migrated IUD.


Assuntos
Remoção de Dispositivo/instrumentação , Remoção de Dispositivo/métodos , Endoscópios , Migração de Dispositivo Intrauterino , Bexiga Urinária/cirurgia , Adulto , China , Cistectomia/instrumentação , Cistectomia/métodos , Cistoscópios , Feminino , Humanos , Histeroscópios , Migração de Dispositivo Intrauterino/efeitos adversos , Dispositivos Intrauterinos/efeitos adversos , Bexiga Urinária/diagnóstico por imagem , Útero/diagnóstico por imagem , Útero/cirurgia
14.
Sheng Li Xue Bao ; 72(2): 148-156, 2020 Apr 25.
Artigo em Zh | MEDLINE | ID: mdl-32328608

RESUMO

The adrenal gland is an important endocrine organ of human body. CYP11B1 gene was specifically expressed in the zona fasciculata in adrenal cortex. In order to better study the function of genes specifically expressed in the zona fasciculata in adrenal cortex, the mice with Cre recombinase specifically expressed in the zona fasciculata in adrenal cortex were constructed. It was then confirmed that CYP11B1 was specifically expressed in adrenal glands. Then, using CRISPR/Cas9 technique, CYP11B1-2A-GfpCre recombinant vector was constructed and subsequently injected into the fertilized eggs of mice. It was confirmed that the Cre gene was mainly expressed in the zona fasciculata in adrenal cortex of CYP11B1Cre mice by using mTmG and LacZ staining. The CYP11B1Cre mice were then mated with cystathionine γ-lyase (CTH)f/f mice, thereby generating CTHf/f/CYP11B1Cre mice. It was also confirmed that CTH gene in the zona fasciculata in adrenal cortex was specifically knocked out in these mice. These results suggest that transgenic mice with specific Cre recombinase expression in the zona fasciculata in adrenal cortex were constructed successfully. This animal model can be a powerful tool for the study of the function of genes expressed in the zona fasciculata in adrenal cortex.


Assuntos
Córtex Suprarrenal/enzimologia , Integrases/metabolismo , Camundongos Transgênicos , Zona Fasciculada/enzimologia , Animais , Sistemas CRISPR-Cas , Cistationina gama-Liase/genética , Integrases/genética , Camundongos
15.
Chemistry ; 25(61): 13972-13976, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31486561

RESUMO

2,4,6-Tri(4-pyridyl)-1,3,5-triazine (tpt) is a widely used ligand for functional coordination compounds. In this work, tpt has shown unprecedented photochromism in the crystalline state. Experimental and theoretical data has revealed that the photocoloration of tpt very likely originates from intramolecular charge separation and the formation of a triplet diradical product. This finding demonstrates a new simple, neutral photochromic molecule and endows the tpt molecule and related compounds with potential optical applications.

16.
Angew Chem Int Ed Engl ; 58(9): 2692-2695, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30614186

RESUMO

Superlattice materials offer new opportunities to modify optical and electrical properties of recently emerging 2D materials. The insertion of tetraethylbenzidine (EtDAB) into interlamination of the established 2D PbI2 semiconductor through a mild solution method yielded the first lead iodide superlattice, EtDAB⋅4PbI2 (EtDAB=tetraethylbenzidine), with radical and non-radical forms. The non-radical form has a non-ionic structure that differs from the common ionic structures for inorganic-organic hybrid lead halides. The radical form shows five orders of magnitude greater conductance and broader photoconductive response range (UV/Vis → UV/Vis-IR), than pure PbI2 and the non-radical form of the superlattice.

17.
Molecules ; 23(9)2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30200213

RESUMO

This study investigated the influence of Canarium album extract (CAext) on intestinal microbiota composition of mice fed a high-fat diet (HFD). Kun Ming (KM) mice were fed either a normal chow diet or a HFD for six weeks. At the seventh week, HFD-fed mice were gavaged daily with saline, or a different dose of CAext for four weeks, respectively. Then, the composition of the gut microbiota was analyzed by high-throughput sequencing technology. Analysis of fecal microbial populations, grouped by phyla, showed significant increases of Firmicutes and Verrucomicrobia, but a decrease of Bacteroidetes in all CAext-fed mice. Particularly, CAext gavage in a low dose or a medium dose caused a significant increase in the proportion of Akkermansia. These findings suggested that CAext can alter the gut microbiota composition of HFD-fed mice, and had a potential prebiotic effects on Akkermansia.


Assuntos
Burseraceae/química , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Animais , Biodiversidade , Dieta Hiperlipídica , Masculino , Camundongos
18.
J Proteome Res ; 16(8): 2863-2876, 2017 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-28665611

RESUMO

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is hereditary cardiomyopathy characterized by the fibro-fatty replacement of the myocardium. A small number of noncomprehensive profiling studies based on human cardiac tissues have been conducted and reported; consequently, ARVC's gene expression pattern characteristics remain largely undocumented. Our study applies large-scaled, quantitative proteomics based on TMT-labeled LC-MS/MS to analyze the left and right ventricular myocardium of four ARVC and four DCM explanted hearts to compare them with normal hearts. Our objective is to reveal the characteristic proteome pattern in ARVC compared with DCM as well as nondiseased heart. We also conducted the RNA sequencing of 10 right ventricles from ARVC hearts paired with four nondiseased donor hearts to validate the proteome results. In a manner similar to that of the well-defined DCM heart failure model, the ARVC model demonstrates the downregulation of mitochondrial function proteins and the effects of many heart failure regulators such as TGFB, RICTOR, and KDM5A. In addition, the inflammatory signaling, especially the complement system, was activated much more severely in ARVC than in DCM. Our most significant discovery was the lipid metabolism reprogramming of both ARVC ventricles in accordance with the upregulation of lipogenesis factors such as FABP4 and FASN. We identified the key upstream regulator of lipogenesis as C/EBPα. Transcriptome profiling verified the consistency with proteome alterations. This comprehensive proteogenomics profiling study reveals that an activation of C/EBPα, along with the upregulation of its lipogenesis targets, accounts for lipid storage and acts as a hallmark of ARVC.


Assuntos
Displasia Arritmogênica Ventricular Direita/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/fisiologia , Metabolismo dos Lipídeos , Miocárdio/metabolismo , Proteogenômica/métodos , Perfilação da Expressão Gênica , Ventrículos do Coração/metabolismo , Humanos , Inflamação , Lipogênese , Proteínas Mitocondriais/metabolismo , Miocárdio/patologia , Transdução de Sinais
19.
Chemistry ; 23(31): 7414-7417, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28425125

RESUMO

N,N'-Disubstituted bipyridinium (viologen) and N-monosubstituted bipyridinium compounds are well known for their electron-transfer (ET) photochromic behavior. Their modification has exclusively focused on the N-substituents to date. For the first time, we have studied the photochromic behavior when one pyridyl ring of the bipyridinium is substituted with a multifunctional azole group, and have found that two new coordination compounds based on N-methyl-4-pyridinium tetrazolate (mptz) zwitterion, [Zn(mptz)2 Br2 ] (1) and [Cd3 (mptz)2 Cl6 ]n ⋅4n H2 O (2), exhibit typical ET photochromic behavior owing to photoinduced ET from halogen anion to the mptz ligand. This work demonstrates a new simple, neutral photoactive molecule with electron-accepting ability, which may act as a photoactive component for materials with potential photoswitching and photocatalysis applications.

20.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 39(5): 643-648, 2017 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-29125106

RESUMO

Objective To investigate the clinical effectiveness of magnetic resonance spectroscopy (MRS) combined with sodium fluorescein(FL) in the treatment of high grade gliomas(HGG). Methods From August 2013 to 2015 November,the clinical data of 72 supratentorial HGG(WHO grade Ⅲ-Ⅳ) patients who had received surgical treatment in our hospital were retrospectively studied,among whom 43 cases received MRS combined with intra-perative FL navigation(observation group),and 29 cases only received conventional surgery(control group). Post-operative radiotherapy and chemotherapy were applied for more than 3 months. Routine enhanced MRI were performed 24-48 hours after the operation to investigate the extent of tumor resection. Six months after the operation,the quality of life of patients was evaluated by using the Karnofsky score,and 1-year postoperative survival rate and progression-free survival(PFS) were observed. Results Postoperative MRI showed that the rate of gross total resection(GTR) in observation group was significantly higher than that in control group(72.09%vs.51.72%;χ2=23.88,P=0.001),and the GTR rate of WHO grade Ⅳ tumors was significantly higher than that of WHO grade Ⅲ tumors in observation group(92.86% vs.62.07%;χ2=6.06,P=0.042). The postoperative Karnofsky score in the observation group was significantly higher than that in control group(µ=2.34,P=0.021). The mean time of follow-up was(16.4±2.4) months(8-21 months) and there was no statistical significant difference between observation group and control group in 1-year survival rate(74.07% vs.77.50%;χ2=4.90,P=0.165) and PFS [(13.2±1.2) months vs.(12.7±2.0) months;χ2=7.26,P=0.067]. In observation group,the PFS of WHO grade Ⅳ patients was significantly higher than that in control group [(14.2±0.3) months vs.(10.0±1.1) months;χ2=11.03,P=0.031]. There was also no statistical significant difference between WHO grade Ⅳ tumors in two groups in terms of 1-year survival rate(71.43% vs.72.54%;χ2=5.33,P=0.089),and there was no statistical significant difference between WHO grade Ⅲ tumors in two groups in 1-year survival rate(75.86% vs. 72.22%;χ2=3.78,P=0.250) and in PFS [(13.7±1.4) months vs.(12.4±0.8) months;χ2=4.85,P=0.083]. Conclusions MRS combined with intraoperative FL navigation technology can improve the resection rate and improve survival quality of patients,and there is no evidence that MRS combined with intraoperative FL navigation prolong the overall survival of patients with high-grade gliomas. Different outcome may be found with longer follow-up and increased simple size.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Glioma/diagnóstico por imagem , Glioma/cirurgia , Imageamento por Ressonância Magnética , Neoplasias Encefálicas/terapia , Intervalo Livre de Doença , Seguimentos , Glioma/terapia , Humanos , Microscopia de Fluorescência , Monitorização Intraoperatória , Qualidade de Vida , Estudos Retrospectivos , Taxa de Sobrevida
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