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1.
Food Chem ; 402: 134225, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36137376

RESUMO

The strong effect of protein digestion products on gastrointestinal-released hormones is recognised. However, little is known about the specific peptide sequences able to induce gastrointestinal hormone secretion and the receptors involved. Our objective was to identify peptides able to induce the secretion of cholecystokinin (CCK) and glucagon like peptide-1 (GLP-1) in the enteroendocrine cell line STC-1, and to evaluate the involvement of the calcium-sensing receptor and G-protein coupled receptor-93 in this cell signalling. The key role of the amino acidic sequence on CCK and GLP-1 secretion is demonstrated. Removing Ser from the N-terminus of κ-casein 33SRYPS37, or the N-terminal Trp-Ile in lysozyme 123WIRGCRL129 decreased the secretion of both hormones. However, substituting Tyr by Ala in peptide αs1-CN 90RYLG93 enhanced the CCK secretion levels but not the GLP-1 ones. In addition, the involvement of CaSR and GPR93 was evidenced, but our results pointed to the contribution of additional receptors or transporters.


Assuntos
Colecistocinina , Hormônios Gastrointestinais , Colecistocinina/genética , Colecistocinina/metabolismo , Colecistocinina/farmacologia , Peptídeo 1 Semelhante ao Glucagon/genética , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Muramidase/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Caseínas/metabolismo , Células Enteroendócrinas , Peptídeos/metabolismo , Hormônios Gastrointestinais/metabolismo , Hormônios Gastrointestinais/farmacologia , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo
2.
Food Chem ; 402: 134354, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36191464

RESUMO

Deciphering interactions between bioactive protein and polyphenols are critical for designing and controlling functional protein-polyphenol complexes. Herein, using the site-directed spin labeled T4 lysozyme (T4L) and rosmarinic acid (RA) as a model system, we combined electron paramagnetic resonance spectra to investigate molecular interaction mechanism of the protein-polyphenol complexes in structural or conformational details. Experimental results show that molecular interactions between T4L and RA are a process from order to disorder. TEM images display that the complexes finally assemble into quasi-spherical colloidal particles. When T4L/RA ratio is 1:1, the complexes exhibit the optimized enzymatic and antioxidant dual-functionalities due to the synergetic effect and protection mechanism. However, with excess addition of RA, the enzymatic and antioxidant activities of the complexes started to attenuate because the catalytic active site and bioactive hydroxyl groups were buried. The revealed high-resolution interaction process could help better understand the corresponding alterations between structure and functionalities.


Assuntos
Muramidase , Polifenóis , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Muramidase/química , Antioxidantes , Marcadores de Spin , Domínio Catalítico , Relação Estrutura-Atividade
3.
Sci Total Environ ; 855: 158648, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36096212

RESUMO

Reducing the water content of waste activated sludge (WAS) is critical for sludge treatment and disposal in wastewater treatment plants (WWTPs). In this study, a new combined conditioning processes by using lysozyme (LZM) and free nitrous acid (FNA) were proposed and demonstrated to enhance the dewaterability of WAS. The water content of sludge cake dropped from 82.82 % to 68.42 % (1 h FNA treatment + 1 h LZM treatment) and 69.52 % (6 h FNA treatment + 1 h LZM treatment) with the combined FNA and LZM treatment; and the corresponding capillary suction time (CST) reduction efficiency increased 49.29 % (1 h FNA treatment + 1 h LZM treatment) and 52.98 % (6 h FNA treatment + 1 h LZM treatment). A comprehensive investigation conducted in this study revealed the underlying mechanism of dewaterability improvement lies in the transformations of extracellular polymeric substances (EPS). The combined conditioning led to enhanced hydrophobicity in the sludge, as suggested by FTIR protein secondary structure and interfacial free energy. The reduced zeta potential and the potential barrier indicated the reduction of the repulsive force of sludge particles and the bound water content in the conditioned floc. The hydrophobicity, flow permeability and flocculability were enhanced after combined treatment, leading to the release of bound water.


Assuntos
Ácido Nitroso , Esgotos , Esgotos/química , Eliminação de Resíduos Líquidos , Muramidase , Água/química , Proteínas
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121864, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36137501

RESUMO

As a kind of phenolic chemical with endocrine disrupting potency, hydroxylated polybrominated diphenyl ethers (OH-PBDEs) cause a latent threat to human health from their residue in the environment. Their binding efficiency with lysozyme (LYSO) was studied by molecular simulation combined with fluorescence, UV-vis absorption and circular dichroism (CD), so as to assess their toxicity at the molecular level. Molecular docking data indicate that van der Waals force is the principal interaction force between OH-PBDEs and LYSO. The binding site for 5'-OH-BDE-25 in LYSO is ascertained as the active site, which interaction with the TRP63 and TRP108 residues of LYSO to take shape a strong face-to-face stacked rank (F-shaped). Both 4'-OH-BDE-99 and 3'-OH-BDE-154 display a certain degree of deviation from the active site. Nevertheless, their F-shaped interaction with TRP63 conduce to bind LYSO and stabilize the docking conformation. Combined with dynamics simulation and spectral analysis, the secondary structure of LYSO can be induced by the three kinds of OH-PBDEs. CD spectrum shows that the combination of LYSO and OH-PBDEs will make α- Helix content increased. The combination of OH-PBDEs and LYSO touch upon a static quenching mechanism as a result of steady state fluorescence. The energy decomposition analysis exhibited that LYSO-OH-PBDEs binding site was stable by van der Waals and hydrophobic interaction. As enzyme activity experiments demonstrate that OH-PBDEs can inhibit the activity of LYSO, which is helpful to clarify the molecular toxicity mechanism of OH-PBDEs.


Assuntos
Éteres Difenil Halogenados , Muramidase , Éteres Difenil Halogenados/análise , Éteres Difenil Halogenados/química , Éteres Difenil Halogenados/metabolismo , Hidroxilação , Modelos Moleculares , Simulação de Acoplamento Molecular , Muramidase/metabolismo , Ligação Proteica
5.
Talanta ; 251: 123789, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35988345

RESUMO

Herein, lysozyme-encapsulated gold nanoclusters (AuNCs@Lzm, AuL) were favorably obtained by a simple and economical synthesis. The resulting AuL exhibits low toxicity, exceptional stability and intense red fluorescence at 650 nm, which can enter living cells and is mainly located in lysosomes. The AuL selectively and sensitively drove to detect folic acid (FA) with a detection limit as low as 0.19 nM based on the combination of the static quenching and the internal filtering effect. Interestingly, the fascinating results discovered that the AuL with ignorable toxicity was adsorbed from the intestine into the liver, and essentially was cleared from the body in 6 days without significant bioaccumulation in zebrafish. Furthermore, the hyaluronic acid (HA) coating AuLH exhibits remarkably targeted tumors towards MCF-7>HeLa > HepG2¼NIH/3T3≈DC, which attributed to the number of receptors expressed by the cells. All these advantages highlight that the AuL is a versatile nanoplatform for sensing, in vivo fluorescence imaging and tumor targeting.


Assuntos
Ouro , Nanopartículas Metálicas , Animais , Ácido Fólico , Ácido Hialurônico , Muramidase , Peixe-Zebra
6.
Methods Mol Biol ; 2570: 197-204, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36156784

RESUMO

The impedimetric detection of a protein, lysozyme (LYS), was carried out herein by aptamer-immobilized single-use pencil graphite electrodes (PGEs). The aptamer was immobilized onto electrochemically activated surface of electrode without using any chemical agents, or any types of nanomaterials. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques were applied to analyze the electrochemical behavior of unmodified PGE and aptamer immobilized PGE. The interaction of aptamer with its target protein, LYS, was then investigated by EIS. The limit of detection for LYS was found to be 1.44 µg/mL (equals to 100.65 nM). The developed aptasensor specific to LYS presented high selectivity against to bovine serum albumin and thrombin.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Grafite , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Eletrodos , Ouro , Grafite/química , Muramidase/química , Prostaglandinas E , Soroalbumina Bovina , Trombina
7.
J Phys Chem B ; 126(44): 9000-9007, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36318974

RESUMO

Protein crystals composed of protein molecules are expected as a novel porous material. They have high porosity, and the knowledge of the diffusion of intracrystalline water is important. In this study, the diffusion coefficient of intracrystalline water in intrinsic hen egg-white lysozyme (HEWL) crystals was determined by a method that combines confocal Raman spectroscopy and air convection with controlled relative humidity. Similar to common porous materials, the drying process of the protein crystals includes three periods: constant-rate drying, falling-rate drying, and equilibrium state. During the falling-rate drying period, the drying rate depends on the diffusion of intracrystalline water in the protein crystal. The gradient of the water content was measured using confocal Raman spectroscopy. The diffusion coefficient of the intrinsic HEWL crystals was determined as 3.1 × 10-7 cm2/s with a water content of 36.3 vol %. The estimated diffusion coefficients of the intrinsic HEWL crystals without cross-linking were in close agreement with those of the cross-linked protein crystals. This study is timely as the knowledge of the intrinsic diffusion coefficient is useful not only for understanding the mechanism of hydration of proteins but also in practical applications such as porous materials, drug binding, and cryoprotectant soaks.


Assuntos
Muramidase , Água , Animais , Muramidase/química , Água/química , Cristalização , Análise Espectral Raman , Galinhas/metabolismo
8.
Molecules ; 27(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36364250

RESUMO

The in vivo potency of polyphosphazene immunoadjuvants is inherently linked to the ability of these ionic macromolecules to assemble with antigenic proteins in aqueous solutions and form physiologically stable supramolecular complexes. Therefore, in-depth knowledge of interactions in this biologically relevant system is a prerequisite for a better understanding of mechanism of immunoadjuvant activity. Present study explores a self-assembly of polyphosphazene immunoadjuvant-PCPP and a model antigen-lysozyme in a physiologically relevant environment-saline solution and neutral pH. Three analytical techniques were employed to characterize reaction thermodynamics, water-solute structural organization, and supramolecular dimensions: isothermal titration calorimetry (ITC), water proton nuclear magnetic resonance (wNMR), and dynamic light scattering (DLS). The formation of lysozyme-PCPP complexes at near physiological conditions was detected by all methods and the avidity was modulated by a physical state and dimensions of the assemblies. Thermodynamic analysis revealed the dissociation constant in micromolar range and the dominance of enthalpy factor in interactions, which is in line with previously suggested model of protein charge anisotropy and small persistence length of the polymer favoring the formation of high affinity complexes. The paper reports advantageous use of wNMR method for studying protein-polymer interactions, especially for low protein-load complexes.


Assuntos
Prótons , Água , Água/química , Muramidase , Polieletrólitos , Difusão Dinâmica da Luz , Calorimetria/métodos , Polímeros/química , Termodinâmica , Espectroscopia de Ressonância Magnética , Adjuvantes Imunológicos
9.
Biomater Sci ; 10(23): 6836-6849, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36321606

RESUMO

The purpose of this study is to provide a new strategy for constructing a temperature-controlled hydrogel as a promising agent for wound healing using natural products through physical co-assembly. Herein, the temperature-controlled physically assembled hydrogel consisting of gallic acid and lysozyme (GL) could be co-assembled into a regular fibrous structure accompanied by strong blue fluorescence with three-dimensional networks at micron levels through hydrophobic interactions, π-π interactions and hydrogen bonding. This GL hydrogel has excellent temperature sensitivity and self-healing properties, as proved by cycle high-low temperature tests. In addition, it possesses stable rheological properties, great sustained release ability, and could realize the spatiotemporal delivery of gallic acid and lysozyme. Biocompatibility and antibacterial tests proved that this well-assembled GL hydrogel has no cytotoxicity but excellent antibacterial activity. Both in vitro and in vivo experiments demonstrated that the GL hydrogel has excellent anti-inflammation efficiency and promotes the healing of chronic wounds by suppressing the expression of pro-inflammatory related genes. Tests using an E. coli-infected wound model confirmed that the GL hydrogel could terminate the inflammatory phase early and ultimately promote the healing of wounds infected by E. coli. This study provides a promising strategy for the effective treatment of wounds through a physical self-assembled hydrogel.


Assuntos
Anti-Infecciosos , Hidrogéis , Hidrogéis/química , Muramidase , Escherichia coli , Ácido Gálico , Preparações de Ação Retardada , Antibacterianos/farmacologia , Antibacterianos/química
10.
Biomolecules ; 12(11)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36358963

RESUMO

The properties of a lysozyme solution under laser-induced breakdown were studied. An optical breakdown under laser action in protein solutions proceeds with high efficiency: the formation of plasma and acoustic oscillations is observed. The concentration of protein molecules has very little effect on the physicochemical characteristics of optical breakdown. After exposure to optical breakdown, changes were observed in the enzymatic activity of lysozyme, absorption and fluorescence spectra, viscosity, and the sizes of molecules and aggregates of lysozyme measured by dynamic light scattering. However, the refractive index of the solution and the Raman spectrum did not change. The appearance of a new fluorescence peak was observed upon excitation at 350 nm and emission at 434 nm at exposure for 30 min. Previously, a peak in this range was associated with the fluorescence of amyloid fibrils. However, neither the ThT assay nor the circular dichroism dispersion confirmed the formation of amyloid fibrils. Probably, under the influence of optical breakdown, a small part of the protein degraded, and a part changed its native state and aggregated, forming functional dimers or "native aggregates".


Assuntos
Amiloide , Muramidase , Muramidase/química , Amiloide/química , Dicroísmo Circular , Difusão Dinâmica da Luz , Lasers
11.
Front Immunol ; 13: 982717, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189245

RESUMO

In recent years, with global warming and increasing marine pollution, some novel marine viruses have become widespread in the aquaculture industry, causing huge losses to the aquaculture industry. Decapod iridescent virus 1 (DIV1) is one of the newly discovered marine viruses that has been reported to be detected in a variety of farmed crustacean and wild populations. Several previous studies have found that DIV1 can induce Warburg effect-related gene expression. In this study, the effects of DIV1 infection on intestinal health of shrimp were further explored from the aspects of histological, enzymatic activities, microorganisms and metabolites using Marsupenaeus japonicus as the object of study. The results showed that obvious injury in the intestinal mucosa was observed after DIV1 infection, the oxidative and antioxidant capacity of the shrimp intestine was unbalanced, the activity of lysozyme was decreased, and the activities of digestive enzymes were disordered, and secondary bacterial infection was caused. Furthermore, the increased abundance of harmful bacteria, such as Photobacterium and Vibrio, may synergized with DIV1 to promote the Warburg effect and induce metabolic reprogramming, thereby providing material and energy for DIV1 replication. This study is the first to report the changes of intestinal microbiota and metabolites of M. japonicus under DIV1 infection, demonstrating that DIV1 can induce secondary bacterial infection and metabolic reprogramming. Several bacteria and metabolites highly associated with DIV1 infection were screened, which may be leveraged for diagnosis of pathogenic infections or incorporated as exogenous metabolites to enhance immune response.


Assuntos
Microbioma Gastrointestinal , Penaeidae , Vibrio , Animais , Antioxidantes , Iridoviridae , Muramidase
12.
Gut Microbes ; 14(1): 2136460, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36288406

RESUMO

Vibrio fluvialis is a halophilic Gram-negative bacterium regarded as an emerging unusual enteric pathogen of increasing public health concern. Our previous work has identified two type VI secretion systems (T6SSs) in V. fluvialis, VflT6SS1, and VflT6SS2, and the latter is functional in mediating interbacterial competitiveness. However, its antibacterial effectors remain to be clarified. In this work, we focused on a new potential effector/immunity pair TssI2/TsiI2. Bioinformatics analysis revealed that the C-terminal domain of TssI2 belongs to a widespread family of pesticin, and its antibacterial toxicity and corresponding protection by TsiI2 were proved via bacterial killing assays, and their action sites were localized to the periplasm of bacterial cells. The interaction of TssI2 and TsiI2 was demonstrated by the bacterial adenylate cyclase two-hybrid, protein pull-down and isothermal titration calorimetry assays. Site-directed mutagenesis demonstrated that, in addition to Glu-844, Thr-863, and Asp-869, which correspond to three reported residues in pesticin of Yersinia pestis, additional residues including Phe-837, Gly-845, Tyr-851, Gly-867, Gln-963, Trp-975, and Arg-1000 were also proved to be crucial to the bactericidal activity of TssI2. Muramidase/lysozyme-related peptidoglycan (PG) hydrolase activities of TssI2 and its variants were validated with permeabilized Escherichia coli cells and purified PG substrate. Based on sequence homologies at C-terminals in various V. fluvialis isolates, TssI2 was subdivided into five clusters (12-22% identity among them), and the antibacterial activities of representative effectors from other four Clusters were also confirmed through periplasmic over-expression in E. coli host. Two selected cognate immunities were proved to confer protection against the toxicities of their effectors. Additionally, TsiI2, which belongs to Cluster I, exhibited cross-protection to effector from Cluster V. Together, current findings expand our knowledge of the diversity and consistency of evolved VgrG effectors in V. fluvialis and on how VflT6SS2 mediates a competitive advantage to gain a better survival.


Assuntos
Microbioma Gastrointestinal , Sistemas de Secreção Tipo VI , Sistemas de Secreção Tipo VI/metabolismo , Periplasma/metabolismo , Muramidase/química , Muramidase/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Peptidoglicano/metabolismo , Adenilil Ciclases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo
13.
J Phys Chem B ; 126(40): 7870-7882, 2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36190807

RESUMO

The impact of pH on proteins is significant but often neglected in molecular dynamics simulations. Constant-pH Molecular Dynamics (CpHMD) is the state-of-the-art methodology to deal with these effects. However, it still lacks widespread adoption by the scientific community. The stochastic titration CpHMD is one of such methods that, until now, only supported the GROMOS force field family. Here, we extend this method's implementation to include the CHARMM36m force field available in the GROMACS software package. We test this new implementation with a diverse group of proteins, namely, lysozyme, Staphylococcal nuclease, and human and E. coli thioredoxins. All proteins were conformationally stable in the simulations, even at extreme pH values. The RMSE values (pKa prediction vs experimental) obtained were very encouraging, in particular for lysozyme and human thioredoxin. We have also identified a few residues that challenged the CpHMD simulations, highlighting scenarios where the method still needs improvement independently of the force field. The CHARMM36m all-atom implementation was more computationally efficient when compared with the GROMOS 54A7, taking advantage of a shorter nonbonded interaction cutoff and a less frequent neighboring list update. The new extension will allow the study of pH effects in many systems for which this force field is particularly suited, i.e., proteins, membrane proteins, lipid bilayers, and nucleic acids.


Assuntos
Simulação de Dinâmica Molecular , Ácidos Nucleicos , Escherichia coli , Humanos , Concentração de Íons de Hidrogênio , Bicamadas Lipídicas , Proteínas de Membrana , Nuclease do Micrococo/química , Muramidase , Tiorredoxinas
14.
Sci Rep ; 12(1): 16906, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207373

RESUMO

Sarcoidosis is a systemic granulomatous disease of unknown etiology with significant heterogeneity in organ manifestations and clinical course. Subjects with sarcoidosis share several features such as, non-necrotizing granuloma, hypergammaglobulinemia, increased local and circulating inflammatory cytokines. Macrophage migration inhibitory factor (MIF) is a pluripotent chemokine modulating cellular function. Study included healthy controls (n = 28) and sarcoidosis patients (n = 65). Sera and BAL of sarcoidosis patients were collected and patients were followed longitudinally for 3 years, and demographics, stages, pulmonary function tests, and organ involvements were recorded. We evaluated MIF in the serum and bronchoalveolar lavage (BAL) fluid of sarcoidosis patients in association with clinical features and cytokines, IL-18, IL-10, IL-6, IFN-γ. We found serum MIF had a positive correlation with IL-10 and IFN-γ and % predicted total lung capacity (%TLC). Serum IL-18 had a significant positive correlation with serum lysozyme, but a negative correlation with %TLC and %DLCO. We identified two groups of sarcoidosis subjects with distinct clinical and cytokine features. A group with prominent extrapulmonary involvement, and low serum MIF, IL-10 and IFN-γ and a group with elevated serum MIF, IL-10 and IFN-γ levels. Our work provides understanding of phenotypic diversity in association with heterogeneity in cytokine landscape in sarcoidosis.


Assuntos
Fatores Inibidores da Migração de Macrófagos , Sarcoidose , Líquido da Lavagem Broncoalveolar , Citocinas , Humanos , Interleucina-10 , Interleucina-18 , Interleucina-6 , Muramidase
15.
Anim Sci J ; 93(1): e13771, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36210498

RESUMO

A bacterial culture of milk is the most common test to determine the presence of mastitis-causing pathogens, which informs appropriate treatment. However, a certain proportion of clinical mastitis milk shows no growth of any mastitis-causing pathogens. We hypothesized that bacterial culture-negative clinical mastitis milk is associated with the activity of antimicrobial components contained in the milk. In this study, the differences in antimicrobial components (lactoferrin, transferrin, lysozyme, lactoperoxidase, and lingual antimicrobial peptide [LAP]) between bacterial culture-positive and culture-negative bovine clinical mastitis milk were investigated using Holstein cows. Our results showed that 37 out of 71 samples of clinical mastitis milk had negative bacterial cultures. The LAP concentration in bacterial culture-negative milk was lower than that in positive milk (31.95 ± 1.64 nM vs. 42.85 ± 4.01 nM). In contrast, the lysozyme concentration in bacterial culture-negative milk was higher than that in positive milk (0.76 ± 0.15 µg/ml vs. 0.42 ± 0.06 µg/ml). In conclusion, the concentration of antimicrobial components was different between bacterial culture-positive and culture-negative bovine clinical mastitis milk, which suggests that antimicrobial components are related to bacterial culture results.


Assuntos
Anti-Infecciosos , Doenças dos Bovinos , Mastite Bovina , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Bactérias , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Feminino , Lactoferrina/metabolismo , Lactoperoxidase/metabolismo , Mastite Bovina/microbiologia , Leite/metabolismo , Muramidase
16.
BMC Med ; 20(1): 353, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36195867

RESUMO

BACKGROUND: Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence. METHODS: We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples. RESULTS: We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1ß, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here. CONCLUSIONS: Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.


Assuntos
Elafina , beta-Defensinas , Feminino , Fator Estimulador de Colônias de Granulócitos , Humanos , Imunoglobulinas , Fatores Imunológicos , Interferons , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-16 , Interleucina-1alfa , Interleucina-6 , Interleucinas , Lactoferrina , Ciclo Menstrual , Muramidase , Progesterona
17.
Nano Lett ; 22(20): 8294-8303, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36239583

RESUMO

Microbial resistance to antibiotics is one of the greatest global healthcare challenges. There is an urgent need to develop effective strategies to overcome antimicrobial resistance. We, herein, report photoinduced in situ growth of a cationic polymer from the N-terminus of lysozyme. The attachment of the cationic polymer improves the proteolytic and thermal stability of lysozyme. Notably, the conjugate can efficiently overcome lysozyme resistance in Gram-positive bacteria and antibiotics-resistance in Gram-negative bacteria, which may be ascribed to the synergistic interactions of lysozyme and the cationic polymer with the bacteria to disrupt their cell membranes. In a rat periodontitis model, the lysozyme-polymer conjugate not only greatly outperforms lysozyme in therapeutic efficacy but also is superior to minocycline hydrochloride, which is the gold standard for periodontitis therapy. These findings may provide an efficient strategy to dramatically enhance the antimicrobial activities of lysozyme and pave a way to overcome antimicrobial resistance.


Assuntos
Antibacterianos , Muramidase , Ratos , Animais , Muramidase/farmacologia , Antibacterianos/farmacologia , Polímeros/farmacologia , Minociclina , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana
18.
Int J Mol Sci ; 23(19)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36232830

RESUMO

Previously, we achieved one-pot fabrication of heparin-immobilized calcium phosphate (CaP) nanoparticles with high dispersibility by a precipitation process in a highly supersaturated reaction solution. In this study, we revealed that the heparin-immobilized CaP nanoparticles have a greater co-immobilizing capacity for basic proteins than for acidic proteins. In this process, heparin acted as not only a particle-dispersing agent but also as an immobilizing agent for basic proteins; it remarkably (approximately three-fold) improved the immobilization efficiency of cytochrome C (a model basic protein) within the CaP nanoparticles. The content of cytochrome C immobilized within the nanoparticles was increased with an increase in cytochrome C concentration in the reaction solution and by aging the nanoparticles. The obtained nanoparticles were dispersed well in water owing to their large negative zeta potentials derived from heparin, irrespective of the content of cytochrome C. Similar results were obtained also for another basic protein, lysozyme, but not for an acidic protein, albumin; the immobilization efficiency of albumin within the nanoparticles was decreased by heparin. These findings provide new insights into the co-immobilization strategy of proteins within heparin-immobilized CaP nanoparticles and will be useful in the design and fabrication of nanocarriers for protein delivery applications.


Assuntos
Nanopartículas , Fosfatos , Albuminas , Fosfatos de Cálcio , Citocromos c , Heparina , Muramidase , Proteínas , Água
19.
Sci Rep ; 12(1): 16632, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36198724

RESUMO

Huangqin Decoction (HQD), a traditional Chinese medicine formula from the Shang Han Lun written by Zhang Zhongjing, has been used in China for nearly two thousand years. According to the traditional Chinese medicine and previous literature, HQD has the effect of clearing heat, removing toxins, relieving diarrhea and pain. Therefore, HQD was used to prevent or cure many diseases, such as inflammation, diarrhea, malaria, and other acute or chronic gastrointestinal diseases. The effect of HQD, one-herb-absent HQD treatments and enrofloxacin (ENR) on the average daily gain (ADG), mortality rates, visceral index and toll-like receptors (TLRs), inflammatory factors and intestinal microflora in E. coli O78-inoculated chicks were investigated. HQD supplementation increased ADG and reduced the mortality rates caused by E. coli challenge, decreased the heart, liver, bursa of Fabricius (BF) and spleen index. HQD supplementation decreased the serum lysozyme (LZM), IL-1ß, TNF-α, IL-10, IL-6 level, down-regulated the mRNA expression of TLR4, -5 and -15 in the spleen by E. coli challenged chicks, and up-regulated the mRNA expression of TLR4, -5 and -15 in BF. At the phylum level, HQD supplementation reversed the increase of Operational Taxonomic Unit (OTUs), decreased the relative abundance of harmful bacteria Proteobacteria, increased the relative abundance of probiotic bacteria Bacteroidetes and Firmicutes. At the genus level, HQD decreased the relative abundance of harmful bacteria Escherichia-Shigella and Pseudomonas. It means that HQD treatment reversed the change of the gut microbiota structure. Compared with HQD, HQD-DZ and HQD-HQ increased the mortality rates. HQD-HQ decreased the ADG and liver index. HQD-GC decreased the spleen index. All herb-absent increased the serum IL-6, but only the HQD-HQ and HQD-SY increased the serum TNF-α. All herb-absent did not activate the TLRs signaling pathways in spleen and BF of chicks. The harmful bacteria Escherichia-Shigella were increased in HQD-HQ and HQD-DZ treatments. HQD-DZ treatment also increased the level of Proteobacteria. The results showed that dietary supplementation with HQD, by down-regulating the mRNA expression of TLR4, -5 and -15 in the spleen, further decreasing the serum LZM and IL-1ß, TNF-α, IL-10, IL-6 level, improves the immune function and reverses the change of fecal microbiome in chicks challenged with E. coli. In herb-absent supplementation, the results showed that SY and DZ play a key role in reducing the levels of inflammatory factors and keeping fecal microbiome balance respectively. More importantly, HQ is indispensable in HQD, not only play a key role in reducing the level of inflammatory factors, but also in keeping the balance of fecal microflora.


Assuntos
Microbioma Gastrointestinal , Scutellaria baicalensis , Animais , Galinhas/microbiologia , Diarreia , Enrofloxacina/farmacologia , Escherichia coli/fisiologia , Imunidade , Interleucina-10/farmacologia , Interleucina-6/farmacologia , Muramidase/farmacologia , RNA Mensageiro/farmacologia , Scutellaria baicalensis/química , Receptor 4 Toll-Like , Fator de Necrose Tumoral alfa/farmacologia
20.
Zhonghua Yi Xue Za Zhi ; 102(37): 2944-2949, 2022 Oct 11.
Artigo em Chinês | MEDLINE | ID: mdl-36207870

RESUMO

Objective: To compare the efficacy of preprotein convertase subtilisin lysozyme 9 (PCSK9) inhibitors with statins in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 140 patients with T2DM (80 males and 60 females) in the People's Hospital Affiliated to Shandong First Medical University from January 2018 to January 2021 were selected, with a mean age of (55±5) years (41-72 years). The patients were divided into observation group (n=68) and control group (n=72) by the random number table method. Both groups were given conventional treatments such as hypoglycemic drugs, the control group was given statins to regulate lipids, and the observation group was given PCSK9 inhibitors to lower lipids. The differences of low-density lipoprotein cholesterol (LDL-C), interleukin (IL)-1, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) expression levels and standard-reaching rate of LDL-C between the two groups were compared. The correlation between serum PCSK9 level and fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and other indicators in T2DM patients was analyzed by Pearson correlation analysis. Results: After treatment, the LDL-C of the observation group was (2.3±0.7) mmol/L, which was lower than that of the control group [(2.7±0.7) mmol/L] (P=0.024); the standard-reaching rate of LDL-C of the observation group was 89.7% (61/68), which was higher than that of the control group [68.1% (49/72)] (P=0.002); the levels of IL-1, IL-6, TNF-, CRP, IL-10 and IL-8 in the observation group after treatment were (27.6±6.6) ng/L, (36.7±6.9) ng/L, (40.1±8.9) ng/L, (7.8±1.8) ng/L, (19.2±3.3) ng/L, (13.7±3.3) ng/L, respectively, which were lower than those in the control group [(30.6±7.9) ng/L, (40.1±7.3) ng/L, (43.4±9.2) ng/L, (10.4±2.5) ng/L, (30.7±3.7) ng/L, (26.8±3.4) ng/L, respectively] (all P<0.05). After treatment, the PCSK9 level in the observation group was (74±13) µg/L, which was lower than that in the control group [(97±14) µg/L] (P<0.001). The level of PCSK9 in T2DM patients was positively correlated with LDL-C, IL-1, IL-6 and TNF-α (r=0.390, 0.433, 0.398 and 0.562, all P<0.05). Conclusion: PCSK9 inhibitors have better lipid-regulating effects in patients with T2DM and can improve the level of inflammation at the same time.


Assuntos
Diabetes Mellitus Tipo 2 , Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Glicemia , Proteína C-Reativa , LDL-Colesterol , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Feminino , Hemoglobina A Glicada/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipoglicemiantes/uso terapêutico , Interleucina-1 , Interleucina-10 , Interleucina-6 , Interleucina-8 , Masculino , Pessoa de Meia-Idade , Muramidase/uso terapêutico , Inibidores de PCSK9 , Pró-Proteína Convertase 9 , Subtilisinas/uso terapêutico , Fator de Necrose Tumoral alfa
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