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1.
J Am Chem Soc ; 146(13): 9224-9229, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38517326

RESUMEN

Ligand-based functionalization strategies have emerged as powerful approaches to tune and optimize blue phosphorescence, which can involve nucleophilic addition to coordinated ligands or electrophilic functionalization via the coordination of exogenous Lewis acids. Whereas both have been used separately to enhance the photophysical properties of organometallic compounds with high-energy triplet states, in this work, we show that these two strategies can be used together on the same platform. Isocyanide-supported cyclometalated platinum compounds undergo nucleophilic addition with diethylamine to form a strong σ-donor acyclic diaminocarbene-supporting ligand. In a subsequent step, a cyanide ancillary ligand is converted into a more strongly π-acidic isocyanoborate via the coordination of a borane Lewis acid. Importantly, both of these ligand-based functionalization steps improve the quantum yields and lifetimes of the blue-phosphorescent complexes. This synergy results in complexes with photoluminescence quantum yields up to 0.40 for deep blue and 0.75 for sky blue regions and PL lifetimes on the order of 10-5 s.

2.
J Am Chem Soc ; 145(2): 1227-1235, 2023 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-36603163

RESUMEN

Ligand-centered functionalization reactions offer diverse strategies to prepare luminescent organometallic compounds. These compounds can have unique structures that are not accessible via traditional coordination chemistry and can possess enhanced or unusual photophysical properties. Here we show that bis-cyclometalated iridium bis-isocyanide complexes (1) react with azide (N3-) to form novel luminescent structures. The fate of the reaction with azide is determined primarily by the substituent on the aryl isocyanide. Those with electron-withdrawing substituents (CF3 or NO2) react with 1 equiv of azide followed by N2 extrusion, forming aryl cyanamido products (2). With electron-donating groups on the aryl isocyanide the reactivity is more diverse, and three outcomes are possible. In two cases, the isocyanide and azide undergo a [3 + 2] cycloaddition to form a C-bound tetrazolato structure (3). In three other cases, 2 equiv of azide are involved in the formation of a previously unobserved structure, where a tetrazolato and aryl cyanamido couple and rearrange to form a chelating ligand comprised of an N-bound tetrazolato and an acyclic diaminocarbene (4). Finally, a bimetallic aryl cyanamido complex (5) is isolated in one case. All compounds are luminescent, some with exceptional photoluminescence quantum yields as high as 0.81 in solution for sky-blue emission, and 0.87 for yellow emission and 0.65 for orange-red emission in polymer films.


Asunto(s)
Iridio , Compuestos Organometálicos , Iridio/química , Azidas , Cianuros/química , Ligandos , Compuestos Organometálicos/química
3.
Inorg Chem ; 62(43): 17843-17850, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37845787

RESUMEN

In this work, we present a series of luminescent platinum acetylide complexes with acetylides that are electronically modified and/or π-extended. Six isocyanide-supported complexes with the general formula cis-[Pt(CNAr)2(C≡CR)2] and six acyclic diaminocarbene (ADC) complexes of the form trans-[Pt(ADC)2(C≡CR)2], all using the same five acetylide ligands, are described. The compounds are characterized by multinuclear NMR, FT-IR, and single-crystal X-ray diffraction. In most cases, the phosphorescence arises from an acetylide-centered 3(π → π*) excited state, although in one of the isocyanide compounds there is evidence for a charge-transfer excited state. The photoluminescence wavelength depends strongly on the substitution pattern and extent of the π conjugation on the acetylide, with maxima spanning the range of ca. 460-540 nm. Most photoluminescence lifetimes are long, beyond 50 µs, and quantum yields are low to moderate, 0.043-0.27. The photoluminescence quantum yields and lifetimes in these compounds do not systematically improve in the ADC complexes compared to the isocyanide versions, suggesting the neutral ligand σ-donor character does not play a large role in the excited-state dynamics when the triplet excited state is delocalized over a large π system.

4.
Inorg Chem ; 62(28): 11278-11286, 2023 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-37410956

RESUMEN

The lack of red and deep-red emitting molecular phosphors with high photoluminescence quantum yields remains a significant fundamental challenge and has implications in optoelectronic technologies for color displays and other consumer products. In this work, we introduce a series of seven new red or deep-red emitting heteroleptic bis-cyclometalated iridium(III) complexes, supported by five different ancillary ligands (L^X) from the salicylaldimine and 2-picolinamide families. Previous work had shown that electron-rich anionic chelating "L^X" ligands can be effective in supporting efficient red phosphorescence, and the complementary approach described here, in addition to being synthetically simpler, offers two key advantages over the previous designs. First, the "L" and "X" functionalities can be independently tuned, providing excellent control over the electronic energy levels and excited-state dynamics. Second, these classes of L^X ligands can have beneficial impacts on the excited-state dynamics but do not significantly perturb the emission color profile. Cyclic voltammetry experiments show that the substituents on the L^X ligand impact the HOMO energy but have a minimal effect on the LUMO energy. Photoluminescence measurements reveal that all the compounds luminesce in the red or deep-red region as a function of the cyclometalating ligand and exhibit exceptionally high photoluminescence quantum yields (ΦPL), comparable or superior to the best-performing red-emitting iridium complexes.

5.
Ann Surg Oncol ; 29(5): 3170-3186, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35175455

RESUMEN

BACKGROUND: This meta-analysis was designed to systematically assess the effectiveness and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) combined with surgery for different stages of advanced gastric cancer (AGC) during the last 12 years. METHODS: The Cochrane Library, PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) were searched online, and papers were retrieved from other sources. Next, randomized controlled trials (RCTs) and high-quality nonrandomized controlled trials (NRCTs) were selected for this analysis. The meta-analysis was conducted with RevMan5.4 software. RESULT: The 10 RCTs and 13 NRCTs selected for the study included 1892 patients. The overall survival rates were higher in the HIPEC group at 1 year (risk ratio [RR], 0.52; P = 0.004) and 3 years (RR, 0.63; P < 0.00001) than in the control group for the patients without peritoneal cancer, and the HIPEC group had a significant reduction in the recurrence rate (RR, 0.60; p < 0.00001). Among the patients with peritoneal carcinomatosis (PC), the HIPEC group had significantly higher overall survival rates at 1 year (RR, 0.62; P = 0.00001), 2 years (RR, 0.85; P = 0.002), and 3 years (RR, 0.87; P = 0.0001), with an increase in the overall median survival time of 4.67 months. The two groups showed no statistically significant difference in terms of complications for patients with PC (RR, 1.03; P = 0.93) or without PC (RR, 1.15; P = 0.51). CONCLUSION: For local AGC without PC, standard surgery combined with prophylactic HIPEC could prolong survival and reduce the recurrence rate without more complications. The prognosis of this treatment strategy for patients with PC is closely related to patient selection. Complete cytoreduction combined with therapeutic HIPEC could prolong survival.


Asunto(s)
Hipertermia Inducida , Neoplasias Peritoneales , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia del Cáncer por Perfusión Regional , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Gástricas/cirugía , Tasa de Supervivencia
6.
Inorg Chem ; 61(23): 8788-8796, 2022 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-35648657

RESUMEN

Formazans have attracted a lot of attention in coordination chemistry since the early 1940s because of their unique properties engendered by the nitrogen-rich conjugated backbone. Although many studies have been done using formazanates to chelate transition metals, research using formazanates as building blocks for polynuclear compounds and supramolecular chemistry remains rare. In this paper, we describe a synthetic strategy that uses a pyridyl-substituted bis(formazanato)nickel complex as a metalloligand to further assemble with two [Ir(C^N)2]+ centers (C^N is the cyclometalating ligand). The trimetallic complexes represent a new binding mode for flexidentate pyridyl-substituted formazanates and a new structural class of polynuclear formazanate complexes. This work expands the chemistry of polynuclear formazanate complexes, for the first time pairing 3d and 5d metals in the same assembly. The redox chemistry of these trimetallic complexes, evaluated via cyclic voltammetry, is described. The compounds described in this work are luminescent, and studies of bis-cyclometalated iridium model complexes lacking the formazanate bridge confirm that the phosphorescence arises from the iridium center.

7.
Chemistry ; 26(51): 11877-11886, 2020 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-32608094

RESUMEN

The utility of flexidentate pyridyl-substituted formazanate ligands for assembling dinuclear coordination complexes with iridium(III) and/or platinum(II) building blocks is demonstrated herein. The dinuclear complexes are prepared either via a stepwise strategy, adding one metal unit at a time, or via one-pot self-assembly. Eight of the new complexes, including both mononuclear precursors and dinuclear products, are structurally characterized by single-crystal X-ray diffraction and NMR spectroscopy, revealing several distinct binding modes of the formazanates. All complexes are characterized by UV/Vis absorption spectroscopy and cyclic voltammetry. The frontier orbitals are primarily localized on the formazanate ligand, and a characteristic, intense formazanate-centered π→π* absorption band is observed in the absorption spectra.

8.
Z Gastroenterol ; 58(2): 137-145, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32050284

RESUMEN

PURPOSE: Rectal neuroendocrine tumors are rare with good prognosis. Several endoscopic methods such as endoscopic polypectomy, endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and modified endoscopic mucosal resection (m-EMR) are used in the treatment of rectal neuroendocrine tumors. Although m-EMR is derived from traditional EMR, it has not been widely used in clinical practice. In this study, we compared the efficacy and safety of EMR and m-EMR in the treatment of rectal neuroendocrine tumors by performing a meta-analysis. MATERIALS AND METHODS: We searched PubMed, Web of Science, and EMBASE index up to the end of January 2017 for all published literature about EMR and m-EMR in the treatment of rectal neuroendocrine tumors. RESULTS: A total of 11 studies involving 811 patients were included. The pooled data suggested that there was a significantly higher rate of histologic complete resection and endoscopic complete resection among patients treated with m-EMR than those treated with EMR (histologic complete resection: OR = 0.23, 95 % CI = 0.10-0.51, p < 0.01; endoscopic complete resection: OR = 0.13, 95 % CI = 0.02-0.74, p = 0.02). The procedure time of EMR was longer than m-EMR (MD = 2.40, 95 % CI = 0.33-4.46, p = 0.02). There was a significantly higher rate of vertical margin involvement among patients treated with EMR than those treated with m-EMR; whereas, there was no significant difference of lateral margin involvement between the m-EMR and EMR groups (vertical margin involvement: OR = 5.00, 95 % CI = 2.67-9.33, p < 0.01; lateral margin involvement: OR = 1.44, 95 % CI = 0.48-4.37, p = 0.52). There was no significant difference in mean tumor size among patients treated with m-EMR versus those treated with EMR (MD = -0.30, 95 % CI = -0.75-0.14, p = 0.18); further, there was no significant difference in endoscopic mean sizes of the tumor and pathological mean sizes of the tumor between the m-EMR and EMR groups (endoscopic mean sizes of the tumor: MD = 0.20, 95 % CI = -0.44-0.84, p = 0.43; pathological mean sizes of the tumor: MD = 0.62, 95 % CI = -0.68-1.92, p = 0.05). No significant differences were detected among the treatment groups with regard to complications (bleeding: OR = 0.87, 95 % CI = 0.39-1.95, p = 0.73; complications (bleeding and perforation): OR = 0.87, 95 % CI = 0.40-1.88, p = 0.73). CONCLUSION: The efficacy of m-EMR are better than EMR among patients undergoing endoscopic treatment of rectal neuroendocrine tumors, and the safety of m-EMR is equivalent to EMR treatment.


Asunto(s)
Resección Endoscópica de la Mucosa/métodos , Endoscopía Gastrointestinal/efectos adversos , Tumores Neuroendocrinos/cirugía , Neoplasias del Recto/cirugía , Humanos , Mucosa Intestinal/patología , Mucosa Intestinal/cirugía , Tumores Neuroendocrinos/patología , Neoplasias del Recto/patología , Estudios Retrospectivos , Resultado del Tratamiento
9.
J Anim Physiol Anim Nutr (Berl) ; 104(3): 831-837, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32166787

RESUMEN

The requirement of net protein (NP) and metabolizable protein (MP) by Dorper crossbred ewe lambs grown from 35 to 50 kg of body weight (BW) was assessed by comparative slaughter experiment. Thirty-five ewe lambs (33.5 ± 0.6 kg BW) of F1 crosses of Dorper × thin-tailed Han sheep were used: 7 lambs were slaughtered as reference animals at the start of the trial, and the remaining 28 lambs were randomly divided into 4 groups of 7 lambs each. Three of the 4 groups were fed a pelleted mixed diet (concentrate/roughage = 44:56, dry matter basis) for ad libitum intake or 65% or 45% of ad libitum intake, and they were all slaughtered when the lambs that were fed ad libitum reached 50 kg BW. The lambs from the fourth group were also fed ad libitum and slaughtered at 43 kg BW as the intermediate group. The intake of MP by the animals of these 4 groups was estimated, and their total body protein and protein retention were measured. The daily requirements of NP and MP for maintenance were 1.52 and 3.98 g/kg BW0.75 , respectively, with a partial efficiency of MP utilization for maintenance of 0.38. The MP requirement for growth ranged from 77.4 to 124.5 g/day for average daily gains from 100 to 250 g BW, and the partial efficiency of MP utilization for growth was 0.66. The Dorper crossbred ewe lambs required more MP for both maintenance and growth in comparison with the recommendations of the US nutritional system.


Asunto(s)
Alimentación Animal/análisis , Dieta/veterinaria , Proteínas en la Dieta/administración & dosificación , Ovinos/fisiología , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Femenino , Necesidades Nutricionales , Ovinos/genética
10.
J Virol ; 92(7)2018 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29321316

RESUMEN

Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) possesses greater replicative capacity and pathogenicity than classical PRRSV. However, the factors that lead to enhanced replication and pathogenicity remain unclear. In our study, an alignment of all available full-length sequences of North American-type PRRSVs (n = 204) revealed two consistent amino acid mutations that differed between HP-PRRSV and classical PRRSV and were located at positions 519 and 544 in nonstructural protein 9. Next, a series of mutant viruses with either single or double amino acid replacements were generated from HP-PRRSV HuN4 and classical PRRSV CH-1a infectious cDNA clones. Deletion of either of the amino acids led to a complete loss of virus viability. In both Marc-145 and porcine alveolar macrophages, the replicative efficiencies of mutant viruses based on HuN4 were reduced compared to the parent, whereas the replication level of CH-1a-derived mutant viruses was increased. Plaque growth assays showed clear differences between mutant and parental viruses. In infected piglets, the pathogenicity of HuN4-derived mutant viruses, assessed through clinical symptoms, viral load in sera, histopathology examination, and thymus atrophy, was reduced. Our results indicate that the amino acids at positions 519 and 544 in NSP9 are involved in the replication efficiency of HP-PRRSV and contribute to enhanced pathogenicity. This study is the first to identify specific amino acids involved in PRRSV replication or pathogenicity. These findings will contribute to understanding the molecular mechanisms of PRRSV replication and pathogenicity, leading to better therapeutic and prognostic options to combat the virus.IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS), caused by porcine reproductive and respiratory syndrome virus (PRRSV), is a significant threat to the global pig industry. Highly pathogenic PRRSV (HP-PRRSV) first emerged in China in 2006 and has subsequently spread across Asia, causing considerable damage to local economies. HP-PRRSV strains possess a greater replication capacity and higher pathogenicity than classical PRRSV strains, although the mechanisms that underlie these characteristics are unclear. In the present study, we identified two mutations in HP-PRRSV strains that distinguish them from classical PRRSV strains. Further experiments that swapped the two mutations in an HP-PRRSV strain and a classical PRRSV strain demonstrated that they are involved in the replication efficiency of the virus and its virulence. Our findings have important implications for understanding the molecular mechanisms of PRRSV replication and pathogenicity and also provide new avenues of research for the study of other viruses.


Asunto(s)
Mutación Missense , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Proteínas no Estructurales Virales , Replicación Viral/genética , Sustitución de Aminoácidos , Animales , Línea Celular , Síndrome Respiratorio y de la Reproducción Porcina/genética , Síndrome Respiratorio y de la Reproducción Porcina/metabolismo , Síndrome Respiratorio y de la Reproducción Porcina/patología , Virus del Síndrome Respiratorio y Reproductivo Porcino/patogenicidad , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Porcinos , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo
11.
Vet Res ; 49(1): 75, 2018 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-30053894

RESUMEN

Porcine reproductive and respiratory syndrome virus (PRRSV) is an important globally distributed and highly contagious pathogen that has restricted cell tropism in vivo and in vitro. In the present study, we found that annexin A2 (ANXA2) is upregulated expressed in porcine alveolar macrophages infected with PRRSV. Additionally, PRRSV replication was significantly suppressed after reducing ANXA2 expression in Marc-145 cells using siRNA. Bioinformatics analysis indicated that ANXA2 may be relevant to vimentin, a cellular cytoskeleton component that is thought to be involved in the infectivity and replication of PRRSV. Co-immunoprecipitation assays and confocal analysis confirmed that ANXA2 interacts with vimentin, with further experiments indicating that the B domain (109-174 aa) of ANXA2 contributes to this interaction. Importantly, neither ANXA2 nor vimentin alone could bind to PRRSV and only in the presence of ANXA2 could vimentin interact with the N protein of PRRSV. No binding to the GP2, GP3, GP5, nor M proteins of PRRSV was observed. In conclusion, ANXA2 can interact with vimentin and enhance PRRSV growth. This contributes to the regulation of PRRSV replication in infected cells and may have implications for the future antiviral strategies.


Asunto(s)
Anexina A2/metabolismo , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Vimentina/metabolismo , Replicación Viral , Animales , Unión Proteica , Porcinos
12.
Vet Res ; 49(1): 103, 2018 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-30290850

RESUMEN

In the original publication of this article [1], the author found the brand of vimentin antibody was wrong in Fig. 3. The legend of Fig. 3, 'mouse anti-vimentin mAb (Cell Signaling Technology) at 4 °C overnight' should be 'mouse anti-vimentin mAb (Sigma-Aldrich) at 4 °C overnight'.

13.
Inorg Chem ; 57(14): 8639-8645, 2018 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-29962201

RESUMEN

Two enantiomeric pairs of new 3d-4f heterometallic clusters have been built from two enantiomer Schiff base derivatives, labeled as R-/ S-H2L, in situ obtained from the condensation reactions with o-vanillin and R-/ S-2-phenylglycinol. The formulas of the series clusters are [Mn6Ln2(µ3-OH)4(µ4-O)(Ac)4(H2O)2( R-L)6]·NO3·OH (Ln = Dy (1R), Gd (2R)), [Mn6Ln2(µ3-OH)4(µ4-O)(Ac)4(H2O)2( S-L)6]·NO3·OH (Ln = Dy (1S), Gd (2S)), whose crystal structures and magnetic properties have been characterized. Structural analysis indicated that the above clusters consisted of a [Mn6Ln2] core, featuring a sandwich configuration. The results of magnetic measurements showed the presence of slow magnetic relaxation with the effective energy barrier of 14.85 K in two Dy derivatives under the condition of zero-dc field, while the significant magnetocaloric effect of Gd analogues was found in a wide temperature range.

14.
BMC Vet Res ; 14(1): 92, 2018 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-29540178

RESUMEN

BACKGROUND: The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has been responsible for several viral attacks in the Asian porcine industry, since the first outbreak in China in 2006. During the early stages of the HP-PRRSV infection, high levels of proinflammatory cytokines are noted in the host peripheral blood, which are accompanied by severe lesions in the lungs and immune system organs; these are considered as the greatest contributors to the overall disease burden. We hypothesized that the anti-PRRSV response in piglets might be mediated by the hypothalamus-pituitary-adrenal (HPA) axis, which led to a decrease in the psycho-neuroendocrinological manifestation of HP-PRRSV etiology via immune response regulation. RESULTS: We investigated the regulation of the HPA axis in HP-PRRSV-infected piglets that were treated with 1 mg/kg body weight (b. w.)/day mifepristone (RU486) or 2 mg/kg b.w./day dexamethasone (DEX). Both RU486 and DEX enhanced the disease status of the piglets infected by the HP-PRRSV HuN4 strain, resulting in high mortality and more severe pathological changes in the lungs. CONCLUSIONS: HP-PRRSV infection activates the HPA axis, and artificial regulation of the immune-endocrine system enhances disease severity in HP-PRRSV-infected piglets. Thus, DEX and RU486 should be avoided in the clinical treatment of HP-PRRS.


Asunto(s)
Sistema Hipotálamo-Hipofisario/fisiología , Síndrome Respiratorio y de la Reproducción Porcina/inmunología , Virus del Síndrome Respiratorio y Reproductivo Porcino/inmunología , Animales , Animales Recién Nacidos/inmunología , Citocinas/sangre , Femenino , Masculino , Sistema Hipófiso-Suprarrenal/fisiología , Síndrome Respiratorio y de la Reproducción Porcina/fisiopatología , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Porcinos/inmunología , Carga Viral/veterinaria
15.
Int J Mol Sci ; 19(10)2018 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-30262770

RESUMEN

In recent years, the overuse of antibiotics has become very serious. Many pathogenic bacteria have become resistant to them, with serious potential health consequences. Thus, it is urgent that we develop new antibiotic drugs. Antimicrobial peptides (AMPs) are important endogenous antibacterial molecules that contribute to immunity. Most have spectral antibacterial properties and do not confer drug resistance. In this paper, an 11-residue peptide (LFcinB18⁻28) with a sequence of KCRRWQWRMKK was modified by amino acid substitution to form a symmetrical amino acid sequence. The antibacterial activities and mechanisms of action of engineered peptides including KW-WK (KWRRWQWRRWK), FP-PF (FPRRWQWRRPF), FW-WF (FWRRWQWRRWF), and KK-KK (KKRRWQWRRKK) were investigated. The four engineered peptides could more effectively inhibit bacteria than the original peptide, LFcinB18⁻28. This suggested that a symmetrical amino acid sequence might enhance the antibacterial activity of AMPs. However, only peptides KW-WK, FP-PF, and KK-KK were safe; FW-WF displayed hemolytic activity. The engineered peptides shared cationic and amphipathic characteristics that facilitated interactions with the anionic microbial membranes, leading to disruption of membrane integrity and permeabilizing microbial membranes, resulting in cell death. Therefore, a symmetrical amino acid sequence and related structural parameters offer an alternative approach to the design of AMPs. This will provide a scientific basis for the design and synthesis of new AMPs.


Asunto(s)
Antibacterianos/síntesis química , Péptidos Catiónicos Antimicrobianos/síntesis química , Lactoferrina/química , Animales , Antibacterianos/farmacología , Antibacterianos/toxicidad , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/toxicidad , Bovinos , Membrana Celular/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Células HEK293 , Humanos , Salmonella/efectos de los fármacos , Staphylococcus/efectos de los fármacos
16.
Molecules ; 23(5)2018 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-29783753

RESUMEN

The primary objective of this study was to improve our understanding of the antimicrobial mechanism of protein-derived peptides and to provide evidence for protein-derived peptides as food bio-preservatives by examining the antimicrobial activities, low cytotoxicity, stabilities, and mechanism of Cp1 (LRLKKYKVPQL). In this study, the protein-derived peptide Cp1 was synthesized from bovine αS1-casein, and its potential use as a food biopreservative was indicated by the higher cell selectivity shown by 11-residue peptide towards bacterial cells than human RBCs. It also showed broad-spectrum antimicrobial activity, with minimum inhibitory concentrations (MICs) of 64⁻640 µM against both gram-positive and gram-negative bacteria. The peptide had low hemolytic activity (23.54%, 512 µM) as well as cytotoxicity. The results of fluorescence spectroscopy, flow cytometry, and electron microscopy experiments indicated that Cp1 exerted its activity by permeabilizing the microbial membrane and destroying cell membrane integrity. We found that Cp1 had broad-spectrum antimicrobial activity, low hemolytic activity, and cytotoxicity. The results also revealed that Cp1 could cause cell death by permeabilizing the cell membrane and disrupting membrane integrity. Overall, the findings presented in this study improve our understanding of the antimicrobial potency of Cp1 and provided evidence of the antimicrobial mechanisms of Cp1. The peptide Cp1 could have potential applications as a food biopreservative.


Asunto(s)
Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Péptidos Catiónicos Antimicrobianos/síntesis química , Péptidos Catiónicos Antimicrobianos/farmacología , Caseínas/química , Animales , Antiinfecciosos/química , Péptidos Catiónicos Antimicrobianos/química , Bovinos , Membrana Celular/efectos de los fármacos , Permeabilidad de la Membrana Celular/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Hemólisis , Humanos , Pruebas de Sensibilidad Microbiana , Pruebas de Toxicidad
18.
Arch Virol ; 162(9): 2715-2726, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28578523

RESUMEN

Porcine circovirus type 2 (PCV2) is the cause of postweaning multisystemic wasting syndrome (PMWS), which encompasses several distinct symptoms in pigs. PCV2 infection and clinical incidence of PMWS have increased in recent years, possibly due to shifts in viral populations and mutations. In this study, we identified PVC2 strains currently afflicting pig populations in mainland China, because this is a prerequisite for developing a specific vaccine to control the spread of PMWS. We collected 235 tissue samples from 16 provinces between 2014 and 2016. Of these, 152 samples were positive for PCV2. We compared the sequences we obtained for the PVC2 capsid gene, ORF2, to those of the Chinese PCV2 sequences deposited in GenBank between 2002 and 2016 (n = 648). Phylogenetic analyses demonstrated that the PCV2d genotype was the most prevalent strain in the sample population included in GenBank and among the positive samples from this study. We also found one PCV2c strain among the GenBank sequences. Furthermore, PCV2a-2F was the predominant genotype in the PCV2a cluster. Amino acid sequence comparisons demonstrated 70.8-100% identity within PCV ORF2 and several consistent mutations in ORF2. More interestingly, six isolates were classified as recombinant strains. Cumulatively, this study represents the first comprehensive description of PCV2 strains distribution, including recent samples, in Chinese porcine populations. We demonstrate the existence of high genetic variability among PVC2 strains and the ability of this virus to rapidly evolve.


Asunto(s)
Circovirus/genética , Síndrome Multisistémico de Emaciación Posdestete Porcino/virología , Enfermedades de los Porcinos/virología , Animales , China/epidemiología , Variación Genética , Genotipo , Mutación , Filogenia , Síndrome Multisistémico de Emaciación Posdestete Porcino/epidemiología , Recombinación Genética , Porcinos , Enfermedades de los Porcinos/epidemiología
19.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 34(4): 572-577, 2017 08 25.
Artículo en Zh | MEDLINE | ID: mdl-29745554

RESUMEN

The objective of the study is to analyze the biological characteristics and stability of the linear derivative Bac2a from bactenecin, compared with the control peptide melittin. The secondary structure, antibacterial activity, hemolytic activity, cell toxicity and stability of the Bac2a were determined by circular dichroism spectroscopy, broth micro-dilution method and MTT assay. The results showed that Bac2a was a nonregular curl in aqueous solution, however, it was an α-helix structure in the hydrophobic environment. The minimal inhibitory concentration (MIC) of Bac2a ranged from 2 to 32 µmol/L, so the bacteriostatic activity of Bac2a was strong. The hemolytic rate was only 14.81% when the concentration of Bac2a was 64 µmol/L, which showed that the hemolytic rate of Bac2a was low. The therapy index of Bac2a was 3.26, and the cytotoxicity was relatively low, thus the cell selectivity was relatively high. In addition, with the heating treatment of 100℃ for 1 h, Bac2a still possessed rather a high antibacterial activity and showed a good heating stability. In a word, Bac2a has good application prospects in food, medicine and other fields, and is expected as a substitute for traditional antibiotics.

20.
J Gen Virol ; 97(6): 1356-1361, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26963602

RESUMEN

Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has been shown to have a wide range of tissue tropism, and can directly and indirectly induce cellular apoptosis. However, the impact of HP-PRRSV infection on the bone marrow (BM) of piglets remains unclear. In this study, we investigated the BM as a novel site of infection by the HP-PRRSV strain in piglets. HP-PRRSV infected SWC3+SWC8- cells in the BM and induced BM cells to undergo apoptosis. The number of apoptotic cells highlights the striking effects of HP-PRRSV on the central immune organs (BM and thymus) that may enhance the susceptibility of pigs to secondary infections and lead to high mortality. This study is, to the best of our knowledge, the first to report the impact of HP-PRRSV on the BM and implicate the depletion of BM cells during HP-PRRSV infection in the development of immunosuppression in this disease.


Asunto(s)
Apoptosis , Células de la Médula Ósea/patología , Células de la Médula Ósea/virología , Síndrome Respiratorio y de la Reproducción Porcina/patología , Virus del Síndrome Respiratorio y Reproductivo Porcino/patogenicidad , Animales , Animales Recién Nacidos , Tolerancia Inmunológica , Porcinos
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