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1.
Molecules ; 26(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652868

RESUMO

Three new 3D metal-organic porous frameworks based on Co(II) and 2,2'-bithiophen-5,5'-dicarboxylate (btdc2-) [Co3(btdc)3(bpy)2]·4DMF, 1; [Co3(btdc)3(pz)(dmf)2]·4DMF·1.5H2O, 2; [Co3(btdc)3(dmf)4]∙2DMF∙2H2O, 3 (bpy = 2,2'-bipyridyl, pz = pyrazine, dmf = N,N-dimethylformamide) were synthesized and structurally characterized. All compounds share the same trinuclear carboxylate building units {Co3(RCOO)6}, connected either by btdc2- ligands (1, 3) or by both btdc2- and pz bridging ligands (2). The permanent porosity of 1 was confirmed by N2, O2, CO, CO2, CH4 adsorption measurements at various temperatures (77 K, 273 K, 298 K), resulted in BET surface area 667 m2⋅g-1 and promising gas separation performance with selectivity factors up to 35.7 for CO2/N2, 45.4 for CO2/O2, 20.8 for CO2/CO, and 4.8 for CO2/CH4. The molar magnetic susceptibilities χp(T) were measured for 1 and 2 in the temperature range 1.77-330 K at magnetic fields up to 10 kOe. The room-temperature values of the effective magnetic moments for compounds 1 and 2 are µeff (300 K) ≈ 4.93 µB. The obtained results confirm the mainly paramagnetic nature of both compounds with some antiferromagnetic interactions at low-temperatures T < 20 K in 2 between the Co(II) cations separated by short pz linkers. Similar conclusions were also derived from the field-depending magnetization data of 1 and 2.


Assuntos
Cobalto/química , Estruturas Metalorgânicas/ultraestrutura , Conformação Molecular , Compostos Organometálicos/química , Adsorção/efeitos dos fármacos , Cristalografia por Raios X , Ligantes , Fenômenos Magnéticos , Estruturas Metalorgânicas/química , Porosidade , Propriedades de Superfície
2.
Nat Biomed Eng ; 5(3): 252-263, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33686281

RESUMO

Contrast agents for magnetic resonance imaging (MRI) improve anatomical visualizations. However, owing to poor image resolution in whole-body MRI, resolving fine structures is challenging. Here, we report that a nanoparticle with a polysaccharide supramolecular core and a shell of amorphous-like hydrous ferric oxide generating strong T1 MRI contrast (with a relaxivity coefficient ratio of ~1.2) facilitates the imaging, at resolutions of the order of a few hundred micrometres, of cerebral, coronary and peripheral microvessels in rodents and of lower-extremity vessels in rabbits. The nanoparticle can be synthesized at room temperature in aqueous solution and in the absence of surfactants, has blood circulation and renal clearance profiles that prevent opsonization, and leads to better imaging performance than Dotarem (gadoterate meglumine), a clinically approved gadolinium-based MRI contrast agent. The nanoparticle's biocompatibility and imaging performance may prove advantageous in a broad range of preclinical and clinical applications of MRI.


Assuntos
Dextranos/química , Compostos Férricos/química , Imagem por Ressonância Magnética/métodos , Nanopartículas/química , Animais , Materiais Biocompatíveis/química , Meios de Contraste/química , Gadolínio/química , Meglumina/química , Camundongos , Camundongos Endogâmicos BALB C , Microvasos/patologia , Compostos Organometálicos/química , Tamanho da Partícula , Polissacarídeos/química , Coelhos , Ratos , Ratos Sprague-Dawley
3.
Sci Rep ; 11(1): 5190, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664450

RESUMO

In Coronavirus disease 2019 (COVID-19) subjects, recent evidence suggests the presence of unique coagulation abnormalities. In this study, we performed clot waveform analyses to investigate whether specific modulations are observed in COVID-19 subjects. We analyzed the second derivative of the absorbance in routine APTT tests performed using an ACL-TOP system. We observed high frequencies of abnormal patterns in APTT second-derivative curves that could be classified into an early shoulder type, a late shoulder type, or a biphasic type, high maximum first-derivative and second-derivative peak levels, and a low minimum second-derivative peak level in COVID-19 subjects. These modulations were not observed in subjects with disseminated intravascular coagulation. These abnormal patterns are also observed in patients with lupus anticoagulant, hemophilia, or factor IX deficiency. The plasma fibrinogen levels might also be involved in the abnormal APTT waveforms, especially the high maximum first-derivative and second-derivative peak levels. The abnormal patterns in the APTT second-derivative curves appear with highest frequency at around 2 weeks after the onset of COVID-19 and were not associated with the severity of COVID-19. These results suggest the possible presence of a specific abnormal coagulopathy in COVID-19.


Assuntos
Coagulação Sanguínea , /sangue , Idoso , Testes de Coagulação Sanguínea , Feminino , Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos , Triazóis
4.
Rev Soc Bras Med Trop ; 54: e0514, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33759920

RESUMO

A 31-year-old male patient developed an ulcer on the glans penis that evolved for three months without healing. We diagnosed it as leishmaniasis using polymerase chain reaction. No immunosuppression or associated diseases were observed. The patient was treated with meglumine antimoniate that cured the lesion in a month post-treatment. Here, we report this case of cutaneous leishmaniasis lesion at the unusual location of glans penis in an immunocompetent individual. The lesion likely developed due to the bite of a vector, highlighting the need for considering cutaneous leishmaniasis among differential diagnosis of sexually transmitted diseases in areas endemic for leishmaniasis.


Assuntos
Antiprotozoários , Leishmaniose Cutânea , Compostos Organometálicos , Adulto , Antiprotozoários/uso terapêutico , Brasil , Genitália , Humanos , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Masculino , Meglumina/uso terapêutico , Antimoniato de Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Reação em Cadeia da Polimerase
6.
Food Chem ; 351: 129248, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33640766

RESUMO

Iron-based metal-organic framework, NH2-MIL-101(Fe), was doped with different dosages of cobalt phthalocyanine nanoparticles (CoPc) to synthesize a series of NH2-MIL-101(Fe)@CoPc nanocomposites. The NH2-MIL-101(Fe)@CoPc nanocomposites were then employed to construct novel impedimetric aptasensors for the detection of ochratoxin A (OTA). Combining the intrinsic advantages of NH2-MIL-101(Fe) (highly porous structure and excellently electrochemical activity) and CoPc (good physiochemical stability and strong bioaffinity), the NH2-MIL-101(Fe)@CoPc nanocomposites show promising properties, which are beneficial for immobilizing OTA-targeted aptamer strands. Amongst, the developed impedimetric aptasensor based on NH2-MIL-101(Fe)@CoPc6:1, prepared using the mass ratio of NH2-MIL-101(Fe):CoPc of 6:1, exhibits the best amplified electrochemical signal and highest sensitivity for detecting OTA. The detection limitation is 0.063 fg·mL-1 within the OTA concentration of 0.0001-100 pg·mL-1, accompanying with high selectivity, good reproducibility and stability, acceptable regenerability, and wide applicability in diverse real samples. Consequently, the proposed sensing strategy can be applied for detecting OTA to cope with food safety.


Assuntos
Técnicas de Química Analítica/instrumentação , Indóis/química , Estruturas Metalorgânicas/química , Nanopartículas/química , Ocratoxinas/análise , Compostos Organometálicos/química , Limite de Detecção , Reprodutibilidade dos Testes
7.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540880

RESUMO

The structures of the adducts formed upon reaction of the cytotoxic paddlewheel dirhodium complex [Rh2(µ-O2CCH3)4] with the model protein hen egg white lysozyme (HEWL) under different experimental conditions are reported. Results indicate that [Rh2(µ-O2CCH3)4] extensively reacts with HEWL:it in part breaks down, at variance with what happens in reactions with other proteins. A Rh center coordinates the side chains of Arg14 and His15. Dimeric Rh-Rh units with Rh-Rh distances between 2.3 and 2.5 Å are bound to the side chains of Asp18, Asp101, Asn93, and Lys96, while a dirhodium unit with a Rh-Rh distance of 3.2-3.4 Å binds the C-terminal carboxylate and the side chain of Lys13 at the interface between two symmetry-related molecules. An additional monometallic fragment binds the side chain of Lys33. These data, which are supported by replicated structural determinations, shed light on the reactivity of dirhodium tetracarboxylates with proteins, providing useful information for the design of new Rh-containing biomaterials with an array of potential applications in the field of catalysis or of medicinal chemistry and valuable insight into the mechanism of action of these potential anticancer agents.


Assuntos
Muramidase/química , Compostos Organometálicos/química , Animais , Antineoplásicos/química , Arginina/química , Sítios de Ligação , Cristalização , Cristalografia por Raios X , Histidina/química , Ligantes , Modelos Moleculares , Estrutura Molecular , Muramidase/metabolismo , Compostos Organometálicos/metabolismo , Ligação Proteica , Conformação Proteica , Solubilidade , Soluções
8.
J Cancer Res Clin Oncol ; 147(5): 1335-1340, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33598797

RESUMO

BACKGROUND: Treatment regimens for patients with metastatic or recurrent post-radiation, locoregional, unresectable salivary cancer are limited. An inverse correlation between somatostatin receptor 2 (SSTR2) and the proliferating marker Ki-67 in neuroendocrine tumors has enabled a treatment plan for metastatic disease, utilizing peptide receptor radionuclide therapy. Interestingly, healthy salivary glands express high levels of SSTR2. In this study, the presence of SSTR2, its correlation with Ki-67 in glandular salivary carcinomas and the clinical applicability thereof was determined. METHODS: In the retrospective part of this study, 76 adequate tumor tissue specimens obtained from patients diagnosed with primary or metastatic salivary carcinomas between 1988 and 2016, were collected for tissue array and histologically classified. Immunohistochemistry was performed to determine the presence, relative expression and potential correlation of SSTR2 and Ki-67. The clinical significance of SSTR2 expression was determined by prospectively assessing 68Ga-DOTATATE uptake using PET-CT imaging, in patients diagnosed with metastatic salivary gland malignant tumors between 2015 and 2016. RESULTS: Sixty-three primary cancer tumors and 14 metastatic tumors were tested. All tumor subtypes were found to express SSTR2 to some extent. The highest expression was seen in Mucoepidermoid carcinoma (MEC) tissues where the majority of specimens (86.4%) expressed SSTR2. A relatively strong immunohistochemical staining score for SSTR2 was observed in MEC, adenoid cystic carcinoma and polymorphous adenocarcinoma. Interestingly, an inverse correlation between SSTR2 and Ki-67 expressions was observed (44%) in MEC tissue. Uptake of 68Ga-DOTATATE was visualized using PET-CT imaging in 40% of patients, across metastatic MEC and ACC. All observations were found to be statistically significant. CONCLUSION: This study confirms the expression of SSTR2 in glandular salivary carcinomas and an inverse correlation in expression levels between SSTR2 and Ki-67. This lays a foundation for novel treatment options in salivary metastatic cancers where SSTR2 may be a potential novel therapeutic target.


Assuntos
Receptores de Somatostatina/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Glândulas Salivares/metabolismo , Adenocarcinoma/metabolismo , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Mucoepidermoide/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Antígeno Ki-67/metabolismo , Masculino , Recidiva Local de Neoplasia/metabolismo , Octreotida/análogos & derivados , Octreotida/metabolismo , Compostos Organometálicos/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/metabolismo , Estudos Retrospectivos
10.
Ecotoxicol Environ Saf ; 213: 112024, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33582410

RESUMO

Combined pollutions of arsenic (As) and copper (Cu) are common in water bodies near mines, non-ferrous metal smelting and power plants. This study investigated the effect of Cu(II) on the absorption and speciation of As(V) by microalgae. We compared the absorption and speciation of arsenic by microalgae (mainly Cyanophyta and Chlorophyta) when exposed to single As(V) with that exposed to As-Cu co-exposure in laboratory. The results showed that in the case of single As(V) exposure, the inhibitory effect of As(V) on microalgae was primarily affected by the exposure time, instead of the concentration of As(V) in the water solution. Compared with single As(V) exposure, the presence of Cu(II) under As-Cu co-exposure promoted the absorption and accumulation of As(V) by algae. The combination effect of As and Cu on algae was antagonistic instead of synergistic within the tolerance range of algae to them. In the presence of Cu(II), more monomethylarsonous acid (MMA) and dimethylarsinous acid (DMA), which are volatile organic arsenic compounds, were produced in algae compared with the control. The finding that Cu(II) can mediate the absorption and speciation processes of arsenic in algae has significance in possible bioremediation of arsenic pollution in aquatic environment.


Assuntos
Arsênico/toxicidade , Cobre/toxicidade , Microalgas/fisiologia , Arsenicais , Ácido Cacodílico/análogos & derivados , Compostos Organometálicos
11.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541948

RESUMO

In this manuscript, we describe a rare case of neuroendocrine tumour metastatic to the testicle, presenting with testicular mass as an isolated symptom. We describe the investigations and management leading us to this uncommon histological diagnosis and explore its significance and impact on further management.


Assuntos
Tumores Neuroendócrinos , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/cirurgia , Testículo/patologia , Colectomia , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/secundário , Orquiectomia , Compostos Organometálicos , Tomografia por Emissão de Pósitrons , Neoplasias Testiculares/patologia , Ultrassonografia
12.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541996

RESUMO

Neuroendocrine tumours (NETs) are rare group of malignancy that originate from neuroendocrine cells present throughout the body. Most patients with NET first present with symptoms associated with metastasis, and up to 20% of patients have unknown primary site of tumour. Most common metastatic sites for small intestine NETs (SI-NETs) are the locoregional lymph nodes and liver. Although mesenteric metastasis through direct extension or lymphatic spread from SI-NETs is common, mesenteric extranodal involvement is extremely rare, and its biology and primary versus secondary nature are not well understood. Due to their small size and location, SI-NETs are frequently undetected on anatomical imaging or indium-111-pentetreotide single-photon emission computed tomography/CT (Octreoscan) and are difficult to be found via endoscopy. Gallium-68-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-octreotate positron emission tomography (68Ga-DOTATATE PET)/CT has been increasingly used for accurate staging, unknown primary tumour site localisation and appropriate management planning. We present a case of an incidentally found mesenteric NET with occult SI-NETs localised preoperatively by 68Ga-DOTATATE PET/CT.


Assuntos
Neoplasias Intestinais/cirurgia , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/secundário , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Idoso , Humanos , Neoplasias Intestinais/patologia , Masculino , Neoplasias Primárias Desconhecidas/patologia , Tumores Neuroendócrinos/patologia , Octreotida/análogos & derivados , Compostos Organometálicos , Compostos Radiofarmacêuticos
13.
Nat Commun ; 12(1): 121, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402676

RESUMO

p97, also known as valosin-containing protein (VCP) or Cdc48, plays a central role in cellular protein homeostasis. Human p97 mutations are associated with several neurodegenerative diseases. Targeting p97 and its cofactors is a strategy for cancer drug development. Despite significant structural insights into the fungal homolog Cdc48, little is known about how human p97 interacts with its cofactors. Recently, the anti-alcohol abuse drug disulfiram was found to target cancer through Npl4, a cofactor of p97, but the molecular mechanism remains elusive. Here, using single-particle cryo-electron microscopy (cryo-EM), we uncovered three Npl4 conformational states in complex with human p97 before ATP hydrolysis. The motion of Npl4 results from its zinc finger motifs interacting with the N domain of p97, which is essential for the unfolding activity of p97. In vitro and cell-based assays showed that the disulfiram derivative bis-(diethyldithiocarbamate)-copper (CuET) can bypass the copper transporter system and inhibit the function of p97 in the cytoplasm by releasing cupric ions under oxidative conditions, which disrupt the zinc finger motifs of Npl4, locking the essential conformational switch of the complex.


Assuntos
Coenzimas/química , Ditiocarb/análogos & derivados , Peptídeos e Proteínas de Sinalização Intracelular/química , Proteínas Nucleares/química , Compostos Organometálicos/química , Ubiquitina/química , Proteína com Valosina/química , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Sítios de Ligação , Clonagem Molecular , Coenzimas/genética , Coenzimas/metabolismo , Microscopia Crioeletrônica , Dissulfiram/química , Dissulfiram/metabolismo , Ditiocarb/química , Ditiocarb/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Modelos Moleculares , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Compostos Organometálicos/metabolismo , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Desdobramento de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidade por Substrato , Ubiquitina/genética , Ubiquitina/metabolismo , Proteína com Valosina/antagonistas & inibidores , Proteína com Valosina/genética , Proteína com Valosina/metabolismo , Dedos de Zinco
14.
Ecotoxicol Environ Saf ; 211: 111917, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33497860

RESUMO

Lead (Pb) is a heavy metal environmental pollutant that can cause functional damage and anemia of immune organs. More and more evidence indicate that the toxicity of lead was related to apoptosis driven by oxidative stress and endoplasmic reticulum stress. This article mainly discusses the protective effect and mechanism of folic acid intervention on lead-induced spleen injury and apoptosis. In this study, Sprague-Dawley rats were randomly divided into control group, lead exposure group (0.2% lead acetate), folic acid + lead group (0.4 mg/kg folic acid and 0.2% lead acetate), and folic acid group (0.4 mg/kg folic acid). By recording and calculating the rat's initial body weight, final body weight, net weight gain, daily weight gain, and spleen index, observe the rat's weight change and spleen weight. And adopt the immunofluorescence staining method to determine the expression level of NrF2, HO-1, GRP78, CHOP protein in the spleen. The results showed that The 0.4 mg/kg folic acid diet did not significantly improve in the body weight and spleen index of lead-exposed rats (P > 0.05). While compared with the control group, the expression levels of HO-1 and CHOP protein were significantly increased in the lead exposure group (P < 0.05), and the expression levels of HO-1 and CHOP protein were significantly reduced in the folic acid intervention group (P < 0.05). In conclusion, lead exposure increased the expression levels of HO-1 and CHOP in the spleen of rats, and caused damage to the spleen. Folic acid down-regulated the expression levels of HO-1 and CHOP proteins through the two pathways of NrF2/HO-1 and GRP78/CHOP, thereby exerting a certain protective effect and alleviating the spleen caused by lead-induced oxidative stress and endoplasmic reticulum stress damage.


Assuntos
Ácido Fólico/farmacologia , Compostos Organometálicos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Baço/efeitos dos fármacos , Acetatos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Ácido Fólico/metabolismo , Chumbo/metabolismo , Masculino , Fator 2 Relacionado a NF-E2 , Ratos , Ratos Sprague-Dawley , Baço/metabolismo , Baço/fisiologia
15.
Molecules ; 26(2)2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33435257

RESUMO

Rollover cyclometalation constitutes a particular case of cyclometallation reaction. This reaction occurs when a chelated heterocyclic ligand loses its bidentate coordination mode and undergoes an internal rotation, after which a remote C-H bond is regioselectively activated, affording an uncommon cyclometalated complex, called "rollover cyclometalated complex". The key of the process is the internal rotation of the ligand, which occurs before the C-H bond activation and releases from coordination a donor atom. The new "rollover" ligand has peculiar properties, being a ligand with multiple personalities, no more a spectator in the reactivity of the complex. The main reason of this peculiarity is the presence of an uncoordinated donor atom (the one initially involved in the chelation), able to promote a series of reactions not available for classic cyclometalated complexes. The rollover reaction is highly regioselective, because the activated C-H bond is usually in a symmetric position with respect to the donor atom which detaches from the metal stating the rollover process. Due to this novel behavior, a series of potential applications have appeared in the literature, in fields such as catalysis, organic synthesis, and advanced materials.


Assuntos
Compostos Organometálicos/química , Compostos Organometálicos/síntese química , Estrutura Molecular
16.
Nat Commun ; 12(1): 114, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414464

RESUMO

Emerging artificial enzymes with reprogrammed and augmented catalytic activity and substrate selectivity have long been pursued with sustained efforts. The majority of current candidates have rather poor catalytic activity compared with natural molecules. To tackle this limitation, we design artificial enzymes based on a structurally well-defined Au25 cluster, namely clusterzymes, which are endowed with intrinsic high catalytic activity and selectivity driven by single-atom substitutions with modulated bond lengths. Au24Cu1 and Au24Cd1 clusterzymes exhibit 137 and 160 times higher antioxidant capacities than natural trolox, respectively. Meanwhile, the clusterzymes demonstrate preferential enzyme-mimicking catalytic activities, with Au25, Au24Cu1 and Au24Cd1 displaying compelling selectivity in glutathione peroxidase-like (GPx-like), catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) activities, respectively. Au24Cu1 decreases peroxide in injured brain via catalytic reactions, while Au24Cd1 preferentially uses superoxide and nitrogenous signal molecules as substrates, and significantly decreases inflammation factors, indicative of an important role in mitigating neuroinflammation.


Assuntos
Enzimas/química , Inflamação , Neurônios/enzimologia , Compostos Organometálicos/química , Animais , Antioxidantes , Encéfalo/enzimologia , Catalase , Catálise , Linhagem Celular , Glutationa Peroxidase/química , Masculino , Metais/química , Camundongos Endogâmicos C57BL , Modelos Moleculares , Neurônios/imunologia , Superóxido Dismutase/química , Superóxidos
17.
Life Sci ; 269: 119066, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33460663

RESUMO

AIMS: This study aimed to investigate the effect of previously synthesized 4,5-diazafluorene derivative (14c) on γδ T cell-mediated cytotoxicity against renal cell carcinoma (RCC). MATERIALS AND METHODS: A real-time cell analyzer monitored cell proliferation, and Cell Counting Kit-8 determined cell viability. A reverse transcription-polymerase chain reaction analyzed gene expression, and protein expression was determined by cellular immunofluorescence analysis and Western blot. KEY FINDINGS: The compound 14c induced the expression of immunomodulatory molecules, such as natural killer group 2, member D ligands (NKG2DLs), fibroblast-associated (Fas) death receptor, and tumor necrosis factor-related apoptosis-inducing ligand receptors (TRAILRs) in RCC. In addition, 14c induced DNA damage responses in RCC. Blocking DNA damage by KU-55933 reduced the effect of γδ T cells on 14c-treated RCC, suggesting that DNA damage responses were involved in the augmentation of γδ T cell-mediated cytotoxicity. Treating 786-O cells with a nitrogen-containing bisphosphonate prodrug further enhanced the anti-tumor effect of γδ T cell plus 14c combination treatment. SIGNIFICANCE: The present evidence indicates that 14c induced DNA damage responses in RCC and augmented γδ T cell-mediated cytotoxicity primarily through NKG2D/NKG2DLs pathways, suggesting potential cancer immunotherapy for harnessing γδ T cells and small compounds that induce DNA damage responses.


Assuntos
Antineoplásicos/farmacologia , Apoptose , Carcinoma de Células Renais/patologia , Citotoxicidade Imunológica/imunologia , Imunidade Celular/imunologia , Compostos Organometálicos/farmacologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Antineoplásicos/química , Compostos Aza/química , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/metabolismo , Proliferação de Células , Dano ao DNA , Fluorenos/química , Humanos , Imunidade Celular/efeitos dos fármacos , Imunomodulação , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/imunologia , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Compostos Organometálicos/química , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Células Tumorais Cultivadas
18.
Clin Nucl Med ; 46(3): e154-e155, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33512839

RESUMO

ABSTRACT: We represent the case of a 61-year-old man with atypical carcinoid tumor of the lung. On posttherapy 177Lu-DOTATATE whole-body scan, focal intense uptake in the inferomedial side of the liver was detected. Pretherapy 68Ga-DOTATATE PET/CT showed no sign of liver metastasis, and posttherapy diagnostic dynamic liver MRI is used to exclude metastatic liver disease. Focal intense uptake was attributed to physiological gallbladder uptake.


Assuntos
Vesícula Biliar/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Octreotida/análogos & derivados , Compostos Organometálicos/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Transporte Biológico , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Octreotida/metabolismo , Imagem Corporal Total
19.
ACS Appl Mater Interfaces ; 13(5): 6615-6630, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33507059

RESUMO

The control of surface wettability through a combination of surface roughness, chemical composition, and structural modification has attracted significant attention for antifogging and antibacterial applications. Herein, a two-step spin-coating method for amphiphilic organic-inorganic hybrid materials with incorporated transition metal ions is presented. The coating solution was prepared via photochemical thiol-ene click reaction between the mercapto functional group in trimethylolpropane tris(3-mercaptopropionate) and the vinyl functionalized silica precursor 3-(trimethoxysilyl)propyl methacrylate. In the first step of coating, a glass substrate was coated using a solution of metal nitrate hydrates and subsequently showed hydrophobic properties. As the second step, the spin-coated glass substrate was further coated with silica nanoparticles (SiO2 NPs) and polycaprolactone triol (PCT) suspension, where the contents of SiO2 NPs were fixed at 0.1 wt %, unless otherwise noted. The coated substrate exhibited hydrophilic properties. For comparison, the coating was also formulated with the SiO2 NPs/PCT suspension without SiO2 NPs and with 0.5 wt % SiO2 NPs as well as by adjusting different coating layer thicknesses. The surface morphology and chemical compositions of the obtained coating materials were analyzed by field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. The transparency and static contact angle of coated samples were measured by UV-visible spectrophotometry and drop shape analysis, respectively. It was concluded that our novel hybrid coating materials exhibited excellent antibacterial and antifogging properties with extremely high scratch resistance and transparency.


Assuntos
Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Escherichia coli/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Tensoativos/farmacologia , Antibacterianos/química , Materiais Revestidos Biocompatíveis/química , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Compostos Organometálicos/química , Tamanho da Partícula , Propriedades de Superfície , Tensoativos/química
20.
ACS Appl Mater Interfaces ; 13(3): 4146-4155, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33440928

RESUMO

Immobilization can be used to improve the stability of lipases and enhances lipase recovery and reusability, which increases its commercial value and industrial applications. Nevertheless, immobilization frequently causes conformational changes of the lipases, which decrease lipase catalytic activity. in the present work, we synthesized UIO-66 and grafted UIO-66 crystals with proline for immobilization of Candida rugosa lipase (CRL). As indicated by steady-state fluorescence microscopy, grafting of proline onto UIO-66 crystals induced beneficial conformational change in CRL. CRL immobilized on UIO-66/Pro (CRL@UIO-66/Pro) demonstrated higher enzyme activity and better recyclability than that immobilized on UIO-66 (CRL@UIO-66) in both hydrolysis (CRL@UIO-66/Pro: 0.34 U; CRL@UIO-66: 0.15 U) and transesterification (CRL@UIO-66/Pro: 0.93 U; CRL@UIO-66: 0.25 U) reactions. The higher values of kcat and kcat/Km of CRL@UIO-66/Pro also showed that it had better catalytic efficiency as compared to CRL@UIO-66. It is also worth noting that CRL@UIO-66/Pro (0.93 U) demonstrated a much higher transesterification activity as compared to free CRL (0.11 U), indicating that UIO-66/Pro has increased the solvent stability of CRL. Both CRL@UIO-66 and CRL@UIO-66/Pro were also used for the fabrication of biosensors for nitrofen with a wide linear range (0-100 µM), lower limit of detection, and good recovery rate.


Assuntos
Lipase/química , Compostos Organometálicos/química , Praguicidas/análise , Éteres Fenílicos/análise , Ácidos Ftálicos/química , Prolina/análogos & derivados , Saccharomycetales/enzimologia , Técnicas Biossensoriais/métodos , Estabilidade Enzimática , Enzimas Imobilizadas/química , Limite de Detecção , Modelos Moleculares
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