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1.
Adv Drug Deliv Rev ; 209: 115327, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38703895

RESUMO

Due to the editability, functionality, and excellent biocompatibility of peptides, in situ self-assembly of peptides in cells is a powerful strategy for biomedical applications. Subcellular organelle targeting of peptides assemblies enables more precise drug delivery, enhances selectivity to disease cells, and mitigates drug resistance, providing an effective strategy for disease diagnosis and therapy. This reviewer first introduces the triggering conditions, morphological changes, and intracellular locations of self-assembling peptides. Then, the functions of peptide assemblies are summarized, followed by a comprehensive understanding of the interactions between peptide assemblies and subcellular organelles. Finally, we provide a brief outlook and the remaining challenges in this field.


Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias , Organelas , Peptídeos , Humanos , Peptídeos/química , Organelas/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Animais
2.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(4): 377-380, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38813631

RESUMO

OBJECTIVE: To investigate the effect of nuclear factor E2-related factor 2 (Nrf2) on the cellular tight junction protein Claudin-18 in endotoxin-induced acute lung injury (ALI). METHODS: Eighteen healthy male C57BL/6 mice were divided into control group, endotoxin-induced ALI model group (ALI group) and Nrf2 activator tert-butylhydroquinone (tBHQ) pretreatment group (tBHQ+ALI group) according to random number table method, with 6 mice in each group. Mice endotoxin-induced ALI model was reproduced by intraperitoneal injection of lipopolysaccharide (LPS, 15 mg/kg), and the mice in the control group was injected with an equal amount of phosphate buffer solution (PBS). The mice in the tBHQ+ALI group received three intraperitoneal injections of tBHQ (a total of 50 mg/kg) at an interval of 1 hour before molding. The last injection of tBHQ was accompanied by LPS of 15 mg/kg. The mice in the control group and model group were given equal amounts of PBS, and PBS or LPS was given at the last injection. The mice were sacrificed at 12 hours after LPS injection to take lung tissues. After the lung tissue was stained with hematoxylin-eosin (HE) staining, the pathological changes were observed under light microscopy, and the lung injury score was calculated. The lung wet/dry ratio (W/D) was determined. Nrf2 protein expression in the lung tissue was detected by Western blotting. Positive expression of Claudin-18 in the lung tissue was determined by immunohistochemistry. RESULTS: The lung tissue showed normal structure, without significant pathological change in the control group. Compared with the control group, the alveolar septum widened accompanied by inflammatory cell infiltration, capillary hyperemia and tissue edema in the ALI group, the lung injury score and lung W/D ratio were significantly increased (lung injury score: 6.50±1.05 vs. 1.83±0.75, lung W/D ratio: 3.79±0.22 vs. 3.20±0.14, both P < 0.01), and the Nrf2 protein expression and Claudin-18 positive expression in the lung tissue were significantly lowered [Nrf2 protein (Nrf2/ß-actin): 0.41±0.33 vs. 1.22±0.33, Claudin-18 (A value): 0.28±0.07 vs. 0.44±0.10, both P < 0.05]. After tBHQ pretreatment, the degree of lung histopathological injury was significantly reduced compared with the ALI group, the alveolar space slightly abnormal, inflammatory cell infiltration and tissue edema reduced, the lung injury score and lung W/D ratio were significantly decreased (lung injury score: 3.00±0.89 vs. 6.50±1.05, lung W/D ratio: 3.28±0.19 vs. 3.79±0.22, both P < 0.01), and Nrf2 protein expression and Claudin-18 positive expression in the lung tissue were significantly increased [Nrf2 protein (Nrf2/ß-actin): 1.26±0.09 vs. 0.41±0.33, Claudin-18 (A valure): 0.45±0.04 vs. 0.28±0.07, both P < 0.05]. CONCLUSIONS: Nrf2 alleviated pulmonary edema and improved endotoxin-induced ALI by up-regulating Claudin-18 expression.


Assuntos
Lesão Pulmonar Aguda , Claudinas , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2 , Animais , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Camundongos , Claudinas/metabolismo , Endotoxinas/efeitos adversos , Endotoxinas/toxicidade , Modelos Animais de Doenças , Lipopolissacarídeos/efeitos adversos , Lipopolissacarídeos/toxicidade , Pulmão/metabolismo , Pulmão/patologia , Regulação para Cima , Junções Íntimas/metabolismo , Hidroquinonas
3.
J Colloid Interface Sci ; 659: 397-412, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38183806

RESUMO

BACKGROUND: Clinical treatments ofgastric infections using antibiotics suffer from the undesired killing of commensal bacteria and emergence of antibiotic resistance. It is desirable to develop pH-responsive antimicrobial peptides (AMPs) that kill pathogenic bacteria such as H. pyloriand resistant E. coli under acidic environment with minimal impact to commensal bacteria whilst not causing antibiotic resistance. EXPERIMENTS: Using a combined approach of cell assays, molecular dynamics (MD) simulations and membrane models facilitating biophysical and biochemical measurements including small angle neutron scattering (SANS), we have characterized the pH-responsive physiochemical properties and antimicrobial performance of two amphiphilic AMPs, GIIKDIIKDIIKDI-NH2 and GIIKKIIDDIIKKI-NH2 (denoted as 3D and 2D, respectively), that were designed by selective substitutions of cationic residues of Lys (K) in the extensively studied AMP G(IIKK)3I-NH2 with anionic residue Asp (D). FINDINGS: Whilst 2D kept non-ordered coils across the entire pH range studied, 3D displayed a range of secondary structures when pH was shifted from basic to acidic, with distinct self-assembly into nanofibers in aqueous environment. Further experimental and modeling studies revealed that the AMPs interacted differently with the inner and outer membranes of Gram-negative bacteria in a pH-responsive manner and that the structural features characterized by membrane leakage and intramembrane nanoaggregates revealed from fluorescence spectroscopy and SANS were well linked to antimicrobial actions. Different antimicrobial efficacies of 2D and 3D were underlined by the interplay between their ability to bind to the outer membrane lipid LPS (lipopolysaccharide), outer membrane permeability change and inner membrane depolarization and leakage. Furthermore, AMP's binding with the inner membrane under acidic condition caused both the dissipation of membrane potential (Δψ) and the continuous dissipation of transmembrane ΔpH, with Δψ and ΔpH being the key components of the proton motive force. Combinations of antibiotic (Minocycline) with the pH-responsive AMP generated the synergistic effects against Gram-negative bacteria only under acidic condition. These features are crucial to target applications to gastric infections, anti-acne and wound healing.


Assuntos
Antibacterianos , Anti-Infecciosos , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/química , Escherichia coli , Bactérias Gram-Negativas , Anti-Infecciosos/farmacologia , Lipopolissacarídeos/química , Bactérias/metabolismo , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana
4.
Clin Sci (Lond) ; 137(18): 1499-1512, 2023 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-37708335

RESUMO

BACKGROUND: Sepsis engenders an imbalance in the body's inflammatory response, with cytokines assuming a pivotal role in its progression. A relatively recent addition to the interleukin-17 family, denominated interleukin-17D (IL-17D), is notably abundant within pulmonary confines. Nevertheless, its implication in sepsis remains somewhat enigmatic. The present study endeavors to scrutinize the participation of IL-17D in sepsis-induced acute lung injury (ALI). METHODS: The levels of IL-17D in the serum and bronchoalveolar lavage fluid (BALF) of both healthy cohorts and septic patients were ascertained through an ELISA protocol. For the creation of a sepsis-induced ALI model, intraperitoneal lipopolysaccharide (LPS) injections were administered to male C57/BL6 mice. Subsequently, we examined the fluctuations and repercussions associated with IL-17D in sepsis-induced ALI, probing its interrelation with nuclear factor erythroid 2-related factor 2 (Nrf2), alveolar epithelial permeability, and heme oxygenase-1. RESULTS: IL-17D levels exhibited significant reduction both in the serum and BALF of septic patients (P<0.001). Similar observations manifested in mice subjected to LPS-induced acute lung injury (ALI) (P=0.002). Intraperitoneal administration of recombinant interleukin 17D protein (rIL-17D) prompted increased expression of claudin 18 and concomitant enhancement of alveolar epithelial permeability, thus, culminating in improved lung injury (P<0.001). Alveolar epithelial type II (ATII) cells were identified as the source of IL-17D, regulated by Nrf2. Furthermore, a deficiency in HO-1 yielded elevated IL-17D levels (P=0.004), albeit administration of rIL-17D ameliorated the exacerbated pulmonary damage resulting from HO-1 deficiency. CONCLUSION: Nrf2 fosters IL-17D production within AT II cells, thereby conferring a protective role in sepsis-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Interleucina-27 , Animais , Humanos , Masculino , Camundongos , Lesão Pulmonar Aguda/tratamento farmacológico , Células Epiteliais Alveolares , Lipopolissacarídeos , Fator 2 Relacionado a NF-E2
5.
Chem Biol Interact ; 374: 110413, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36804394

RESUMO

PTEN-induced putative kinase 1 (PINK1) is a mitochondrial kinase that protects against oxidative stress-induced cellular death. PINK1 deletion, on the other hand, disrupts mitochondrial calcium (Ca2+) homeostasis in various brain disorders. This study looked at how PINK1 affects hippocampal intracellular Ca2+ changes in mice with septic encephalopathy. Mice were injected intraperitoneally with lipopolysaccharide (LPS, 5 mg/kg) to induce septic encephalopathy; then, fiber photometry was used to record hippocampal Ca2+ transients during behavioral tests in freely moving mice. Basal cytoplasmic Ca2+ levels were detected under a fluorescent microscope. LPS induced PINK1 expression and neuronal loss in the hippocampus of mice, whereas no difference in neuronal counts was shown between PINK1 knockout LPS mice and WT LPS mice. PINK1 deficiency led to inhibited Ca2+ transients and increased intracellular Ca2+ levels in the hippocampus of mice, thus, significantly aggravating the cognitive dysfunction in septic mice. An analysis of Parkin and PLC-γ1, downstream effectors of PINK1, showed that they are associated with the effects of PINK1. These results demonstrate that PINK1 deficiency disrupts intracellular Ca2+ homeostasis and exacerbates septic encephalopathy. This observation suggests a protective role of PINK1 in septic encephalopathy.


Assuntos
Encefalopatias , Proteínas Quinases , Animais , Camundongos , Encefalopatias/metabolismo , Hipocampo/metabolismo , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Neurônios/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo
6.
J Colloid Interface Sci ; 637: 182-192, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36701864

RESUMO

HYPOTHESIS: It is widely regarded that antimicrobial peptides (AMPs) kill bacteria by physically disrupting microbial membranes and causing cytoplasmic leakage, but it remains unclear how AMPs disrupt the outer membrane (OM) of Gram-negative bacteria (GNB) and then compromise the inner membrane. We hypothesise that different AMPs impose different structural disruptions, with direct implications to their antimicrobial efficacies. EXPERIMENTS: The antimicrobial activities of three typical AMPs, including the designed short AMP, G3, and two natural AMPs, melittin and LL37, against E. coli and their haemolytic activities were studied. Lipopolysaccharide (LPS) and anionic di-palmitoyl phosphatidyl glycerol (DPPG) monolayer models were constructed to mimic the outer membrane and inner membrane leaflets of Gram-negative bacteria. The binding and penetration of AMPs to the model lipid monolayers were systematically studied by neutron reflection via multiple H/D contrast variations. FINDING: G3 has relatively high antimicrobial activity, low cytotoxicity, and high proteolytic stability, whilst melittin has significant haemolysis and LL37 has weaker antimicrobial activity. G3 could rapidly lyse LPS and DPPG monolayers within 10-20 min. In contrast, melittin was highly active against the LPS membrane, but the dynamic process lasted up to 80 min, with excessive stacking in the OM. LL37 caused rather weak destruction to LPS and DPPG monolayers, leading to massive adsorption on the membrane surface without penetrating the lipid tail region. These findings demonstrate that the rationally designed AMP G3 was well optimised to impose most effective destruction to bacterial membranes, consistent with its highest bactericidal activity. These different interfacial structural features associated with AMP binding shed light on the future development of active and biocompatible AMPs for infection and wound treatments.


Assuntos
Anti-Infecciosos , Lipopolissacarídeos , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/química , Peptídeos Antimicrobianos , Meliteno/farmacologia , Meliteno/metabolismo , Escherichia coli/metabolismo , Anti-Infecciosos/química , Bactérias Gram-Negativas/metabolismo , Bactérias/metabolismo , Membrana Celular/metabolismo , Antibacterianos/química
7.
Small ; 19(3): e2204428, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36417574

RESUMO

Recent developments in antimicrobial peptides (AMPs) have focused on the rational design of short sequences with less than 20 amino acids due to their relatively low synthesis costs and ease of correlation of the structure-function relationship. However, gaps remain in the understanding of how short cationic AMPs interact with the bacterial outer and inner membranes to affect their antimicrobial efficacy and dynamic killing. The membrane-lytic actions of two designed AMPs, G(IIKK)3 I-NH2 (G3 ) and G(IIKK)4 I-NH2 (G4 ), and previously-studied controls GLLDLLKLLLKAAG-NH2 (LDKA, biomimetic) and GIGAVLKVLTTGLPALISWIKRKR-NH2 (Melittin, natural) are examined. The mechanistic processes of membrane damage and the disruption strength of the four AMPs are characterized by molecular dynamics simulations and experimental measurements including neutron reflection and scattering. The results from the combined studies are characterized with distinctly different intramembrane nanoaggregates formed upon AMP-specific binding, reflecting clear influences of AMP sequence, charge and the chemistry of the inner and outer membranes. G3 and G4 display different nanoaggregation with the outer and inner membranes, and the smaller sizes and further extent of insertion of the intramembrane nanoaggregates into bacterial membranes correlate well with their greater antimicrobial efficacy and faster dynamic killing. This work demonstrates the crucial roles of intramembrane nanoaggregates in optimizing antimicrobial efficacy and dynamic killing.


Assuntos
Anti-Infecciosos , Peptídeos Antimicrobianos , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Anti-Infecciosos/farmacologia , Bactérias , Simulação de Dinâmica Molecular
8.
J Colloid Interface Sci ; 630(Pt B): 911-923, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36368131

RESUMO

HYPOTHESIS: Designed antimicrobial lipopeptides (ALPs) offer the attractive benefits of short peptide sequences and flexible tuning of amphiphilicity by altering the acyl chain length. These lipopeptides kill microbes by forming intriguing in-membrane nanostructures and causing the leakage of internal contents. However, how subtle differences in the molecular structures of the lipopeptides affect their antimicrobial efficacy and biocompatibility to host cells is still under-investigated. EXPERIMENTS: This work focuses on assessing changes in the acyl chain length of CH3(CH2)n-2CO-KKKIII-NH2 (n = 10, 12 and 14, K = lysine, I = isoleucine, denoted as CnKI3) on the antimicrobial potency and cytotoxicity by combining biological assays with physical measurements. Aggregation properties were characterized by changes in critical aggregation concentration (CAC) from surface tension measurements. Antimicrobial susceptibility tests, cytotoxic MTT assays, haemolytic tests, and dynamic bactericidal experiments were employed to reveal their bioactive potency toward different types of cells. To further investigate lipopeptides' underlying antimicrobial and cytotoxic mechanisms, lipid monolayer and lipid small unilamellar vesicle (SUV) models were established and biophysically characterized. FINDINGS: An increase in n led to the decrease in the CAC of CnKI3, showing a rising membrane-lytic power. Subsequent bioactive measurements revealed the optimal performance of C12KI3 from this series of lipopeptides. The selective membrane binding behaviour was well supported by neutron reflection data from charged lipid monolayer models, revealing membrane-supported nanostructures of ALPs. However, increased membrane-lytic actions in C14KI3 led to notably increased toxicity and reduced selectivity. On the other hand, C14KI3 can impose faster dynamic killing than natural lipopeptide polymyxin B, showing the distinct impact of the amphiphilic balance from the designed lipopeptide. In contrast, the distinctly weaker binding to zwitterionic membrane models (monolayers and SUVs) provided direct nanoscale structural evidence to the mildness of the designed ALPs on host cells. This work demonstrates the high selectivity and fast killing of rationally designed short ALPs to microbes via in-membrane nanostructuring.


Assuntos
Anti-Infecciosos , Lipopeptídeos , Lipopeptídeos/farmacologia , Lipopeptídeos/química , Antibacterianos/farmacologia , Antibacterianos/química , Tensão Superficial , Sequência de Aminoácidos
9.
Clin Interv Aging ; 17: 1751-1760, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36479561

RESUMO

Purpose: To investigate the effect of transcutaneous electrical acupoint stimulation (TEAS) on urinary retention after laparoscopic cholecystectomy in elderly patients, and to explore the relationship between TEAS and urinary ATP. Patients and Methods: The TEAS group was administered active TEAS at specific acupuncture points prior to induction of anesthesia and continued for 45 mins after surgery. In the control group, participants received sham stimulus at the same acupoints and no output current was delivered by disconnecting the device's output line. Urine samples were collected and evaluated in the first spontaneous voiding after surgery. In this study, postoperative urinary retention (POUR) was the primary outcome, which was diagnosed based on clinical symptoms, ultrasound assessments, and the need for bladder catheterization. Secondary outcomes include urinary ATP, postoperative spontaneous urination, urination symptoms, catheter-related bladder discomfort (CRBD), delirium, duration and hospitalization costs. Results: The study involved 598 patients recruited and randomized between August 2018 and June 2020. Among these patients, 547 (91.5%) completed the study and were analyzed. There were 64 cases of POUR, including 23 (8.4%, 95% confidence interval [CI]: 6.4-9.9%) in the TEAS group and 41 (15.0%, 95% CI: 9.3-13.4%) in the control group (p = 0.017). A significant difference was observed between the TEAS and control groups for urinary ATP concentration in the first spontaneous urine postoperatively (344 nmol/L versus 233 nmol/L, p=0.001). There was a shorter spontaneous voiding recovery time, smaller voiding threshold, less postoperative catheterization, less CRBD, and lower hospitalization costs in TEAS group compared with control group. Conclusion: TEAS reduces the incidence of POUR in elderly patients undergoing laparoscopic cholecystectomy, which may be related to an increase in bladder ATP release.


Assuntos
Retenção Urinária , Humanos , Idoso , Retenção Urinária/etiologia , Retenção Urinária/terapia , Estudos Prospectivos , Estimulação Elétrica , Trifosfato de Adenosina
10.
Biochem Biophys Res Commun ; 624: 164-170, 2022 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-35952538

RESUMO

Electroacupuncture (EA) can protect against acute urinary retention (AUR); however, the underlying mechanism remains unclear. Non-vesicular ATP release mediated by transient receptor potential (TRP) channels were identified as a key contributor to signaling in urothelial cells. In this study, the AUR model was established by urethral outlet obstruction in female Sprague-Dawley rats. EA was performed at SP6 and BL32 for 0.5 h prior to induction of AUR. EA reduced TRPV1 expression and urinary ATP concentrations in rat bladder, decreased the peak intravesical pressure during AUR, and attenuated abnormal voiding patterns and bladder pathological injury induced by AUR. Besides, 179 patients who experienced postoperative urinary retention were recruited and found that EA reduced urinary ATP concentrations and accelerated the recovery of spontaneous voiding. These observations indicate that EA exerts protection against AUR-induced bladder dysfunction by reducing urinary ATP concentrations through the regulation of TRPV1.


Assuntos
Eletroacupuntura , Retenção Urinária , Trifosfato de Adenosina/metabolismo , Animais , Feminino , Humanos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Canais de Cátion TRPV/metabolismo , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Doenças da Bexiga Urinária/prevenção & controle , Doenças da Bexiga Urinária/terapia , Retenção Urinária/complicações , Retenção Urinária/etiologia , Retenção Urinária/metabolismo
11.
J Colloid Interface Sci ; 623: 368-377, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35594595

RESUMO

HYPOTHESIS: Acyl-l-carnitines (CnLCs) are potentially important as biosurfactants in drug delivery and tissue engineering due to their good biocompatibility. However, little is currently known about the basic interfacial behavior underlying their technological applications. Following our previous characterization of their solution aggregation and adsorption at the air/water interface, this work examines how they adsorb at the hydrophilic solid/liquid interface. EXPERIMENTS: As the SiO2/water interface has served as the model substrate for many interfacial adsorption studies, so it has been used in this work as the solid substrate to facilitate dynamic adsorption by spectroscopic ellipsometry (SE) and structural determination of the adsorbed layers by neutron reflection (NR) under different conditions at the SiO2/water interface from a group of CnLC (n = 12, 14, and 16). FINDINGS: CnLC surfactants are zwitterionic at neutral pH. They reached saturated adsorption above their critical micellar concentrations (CMCs) and formed a sandwich bilayer with a head-tail-head structure at the hydrophilic SiO2/water interface. The total thicknesses of the adsorbed layers at CMC were found to be 33 ± 2, 35 ± 2, and 37 ± 2 Å for C12LC, C14LC, and C16LC, respectively, with their inner and outer head layers remaining similar but the thickness of the interdigitated middle layer increasing with acyl chain length. As the solution becomes acidic, the carboxyl groups become protonated and the l-carnitine heads are net positively charged, resulting in increased repulsion between the head groups. In this situation, the CnLC surfactants are adsorbed as distinct aggregates to reduce repulsive interaction, resulting in reduced surfactant volume fraction and layer thickness. However, a high ionic strength can screen the repulsive interaction and enhance the adsorbed amount, effectively diminishing the impact of pH. This information provides a useful basis for exploring the technological applications of CnLCs involving a solid substrate.


Assuntos
Dióxido de Silício , Tensoativos , Adsorção , Carnitina , Dióxido de Silício/química , Tensoativos/química , Água/química
12.
Langmuir ; 38(21): 6623-6637, 2022 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-35587380

RESUMO

Cationic biocides have been widely used as active ingredients in personal care and healthcare products for infection control and wound treatment for a long time, but there are concerns over their cytotoxicity and antimicrobial resistance. Designed lipopeptides are potential candidates for alleviating these issues because of their mildness to mammalian host cells and their high efficacy against pathogenic microbial membranes. In this study, antimicrobial and cytotoxic properties of a de novo designed lipopeptide, CH3(CH2)12CO-Lys-Lys-Gly-Gly-Ile-Ile-NH2 (C14KKGGII), were assessed against that of two traditional cationic biocides CnTAB (n = 12 and 14), with different critical aggregation concentrations (CACs). C14KKGGII was shown to be more potent against both bacteria and fungi but milder to fibroblast host cells than the two biocides. Biophysical measurements mimicking the main features of microbial and host cell membranes were obtained for both lipid monolayer models using neutron reflection and small unilamellar vesicles (SUVs) using fluorescein leakage and zeta potential changes. The results revealed selective binding to anionic lipid membranes from the lipopeptide and in-membrane nanostructuring that is distinctly different from the co-assembly of the conventional CnTAB. Furthermore, CnTAB binding to the model membranes showed low selectivity, and its high cytotoxicity could be attributed to both membrane lysis and chemical toxicity. This work demonstrates the advantages of the lipopeptides and their potential for further development toward clinical application.


Assuntos
Anti-Infecciosos , Desinfetantes , Animais , Antibacterianos/química , Anti-Infecciosos/toxicidade , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/toxicidade , Desinfetantes/farmacologia , Lipopeptídeos/farmacologia , Mamíferos , Testes de Sensibilidade Microbiana
13.
J Colloid Interface Sci ; 618: 78-87, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35334364

RESUMO

HYPOTHESIS: Nonionic alkyl ethoxylate surfactants are widely used in agrochemicals to facilitate the permeation of systemic herbicides and fungicides across the plant waxy film. Industrial grade surfactants are often highly mixed and how the mixing affects their interactions with pesticides and wax films remains largely unexplored. A better understanding could enable design of mixed nonionic surfactants for herbicides and fungicides to maximize their efficiency and reduce wastage whilst controlling their impact on plant wax films. EXPERIMENT: In this study, nonionic surfactants with general structure n-oxyethylene glycol monododecyl ether (C12En) were used to form surfactant mixtures with the same average ethoxylate numbers but different hydrophilic-lipophilic balance (HLB) values. Their mixed micellar systems were then used to solubilize a herbicide diuron (DN) and a fungicide cyprodinil (CP), followed by plant wax solubilization upon contact with wax films. These processes were monitored by 1H NMR and SANS. FINDING: Pesticide solubilization made surfactant micelles effectively more hydrophobic but subsequent wax dissolution caused pesticide release and the restoration of the micellar amphiphilicity. Nonionic surfactants with lower HLBs form larger nanoaggregates, show enhanced wettability, and have better ability to solubilize and permeate pesticides across the wax film, but may cause significant damage to plant growth. These observations help explain why herbicides applied on weeds would benefit from surfactants with lower HLB values while fungicides require surfactants with HLBs to balance between delivery efficiency and potential phytotoxicity risks.


Assuntos
Fungicidas Industriais , Herbicidas , Praguicidas , Herbicidas/química , Micelas , Praguicidas/química , Solubilidade , Tensoativos/química , Ceras
14.
Front Endocrinol (Lausanne) ; 13: 812974, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250871

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is a common and severe social problem. Erectile dysfunction (ED) is an important health concern. The prevalence of OSA with ED is increasing, which significantly affects the quality of life and work efficiency of patients. However, the mechanism underlying the comorbidity of these two diseases remains unclear. OBJECTIVES: (1) Investigate the prevalence of OSA with ED; (2) analyze the correlation between OSA and ED; and (3) explore the treatment response to and possible mechanism of uvulapalatopharyngoplasty (UPPP) in patients with OSA and ED. This study aims to provide a theoretical basis for the clinical diagnosis and comprehensive treatment of OSA with ED and improve prevention and treatment strategies. MATERIALS AND METHODS: In total, 135 subjects were enrolled in the study. Clinical data, polysomnography, the ESS score, Beck anxiety score, Beck depression score, IIEF-5 score and ASEX score were recorded before UPPP and 6 months after UPPP. Sex hormones were measured for all subjects using a Roche electrochemiluminescence analyzer. RESULT: The prevalence of OSA with ED was 64.52%, and the prevalence of severe OSA with ED was 73.02%. The prevalence of OSA with ED increased with age, BMI and apnea-hypopnea index (AHI) value. Among polysomnography indicators, minimum oxygen saturation and average oxygen saturation may predict the occurrence of OSA with ED. Improving the patient's anxiety and depression is very important for treating OSA with ED. Sex hormone levels were not significantly correlated with the occurrence of OSA with ED. CONCLUSION: ED is a common symptom of OSA patients. This study showed that sex hormone levels in OSA patients with ED were not significantly correlated with the condition, but further investigation of this relationship is worthwhile. It is recommended that the free and combined types of sex hormones be further distinguished during testing because the free type is the active form. UPPP surgical treatment is effective for OSA with ED, and its possible mechanism is protection of the peripheral nerves of the sex organs by improving nighttime hypoxia and arousal.


Assuntos
Disfunção Erétil , Apneia Obstrutiva do Sono , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Hormônios Esteroides Gonadais , Humanos , Masculino , Prevalência , Qualidade de Vida , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia
15.
J Colloid Interface Sci ; 609: 491-502, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34863541

RESUMO

HYPOTHESIS: l-carnitines in our body systems can be readily converted into acyl-l-carnitines which have a prominent place in cellular energy generation by supporting the transport of long-chain fatty acids into mitochondria. As biocompatible surfactants, acyl-l-carnitines have potential to be useful in technical, personal care and healthcare applications. However, the lack of understanding of the effects of their molecular structures on their physical properties has constrained their potential use. EXPERIMENTS: This work reports the study of the influence of the acyl chain lengths of acyl-l-carnitines (CnLC) on solubility, surface adsorption and aggregation. Critical micellar concentrations (CMCs) of CnLC were determined by surface tension measurements. Neutron reflection (NR) was used to further examine the structure and composition of the adsorbed CnLC layer. The structural changes of the micellar aggregates under different concentrations of CnLC, pH and ionic strength were determined by dynamic light scattering (DLS) and small angle neutron scattering (SANS). FINDINGS: C12LC is fully soluble over a wide temperature and concentration range. There is however a strong decline of solubility with increasing acyl chain length. The adsorption and aggregation behavior of C14LC was therefore studied at 30 °C and C16LC at 45 °C. The solubility boundaries displayed distinct hysteresis with respect to heating and cooling. The CMCs of C12LC, C14LC and C16LC at pH 7 were 1.1 ± 0.1, 0.10 ± 0.02 and 0.010 ± 0.005 mM, respectively, with the limiting values of the area per molecule at the CMC being 45.4 ± 2, 47.5 ± 2 and 48.8 ± 2 Å2 and the thicknesses of the adsorbed CnLC layers at the air/water interface increasing from 21.5 ± 2 to 22.6 ± 2 to 24.2 ± 2 Å, respectively. All three surfactants formed core-shell spherical micelles with comparable dimensional parameters apart from an increase in core radius with acyl chain length. This study outlines the effects of acyl chain length on the physicochemical properties of CnLCs under different environmental conditions, serving as a useful basis for developing their potential applications.


Assuntos
Micelas , Tensoativos , Adsorção , Espalhamento a Baixo Ângulo , Tensão Superficial
16.
Front Pediatr ; 9: 598063, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33869109

RESUMO

The relationship between eosinophils/basophils and allergic sensitization is not clear in pediatric adenotonsillar hypertrophy (ATH). The objective of this study is to investigate the relationship between eosinophil/basophil counts and peripheral specific IgE levels, and identify the common allergens in children with ATH. We initially screened 1,031 consecutive children who underwent adenotonsillectomy in our department from June 2018 to June 2019, and finally included 676 children. The eosinophil count, basophil count, and levels of specific IgE were collected. Correlations between two quantitative variables were assessed using the Pearson or Spearman coefficient. Logistic regression analyses were performed to evaluate the odds ratios (ORs) for atopy after controlling for age, sex, vitamin D, BMI, and visiting season. Both the eosinophil and basophil counts in atopic participants were significantly higher compared to non-atopic participants. The eosinophil count correlated with the levels of IgE specific to all allergens, and eosinophilia was independently associated with all tested atopy allergens other than atopy to dander after multivariate adjustment. Additionally, the basophil count correlated with the IgE levels specific to A. alternate and food mix, and basophilia was still significantly associated with atopy to food mix after multivariable adjustment. Furthermore, among allergic participants, D. farinae was the most prevalent allergen, followed by food mix, D. pteronyssinus, and A. alternata. In conclusion, eosinophils were more relevant to allergic sensitization than basophils, with eosinophils being significantly associated with all tested atopy allergens apart from dander, and basophils being associated with atopy to food mix. Furthermore, D. farinae was the most prevalent allergen and may be indicative of desensitization therapy.

17.
Curr Opin Colloid Interface Sci ; 52: 101417, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33642918

RESUMO

Since the outbreak of the COVID-19 pandemic, most countries have recommended their citizens to adopt social distance, hand hygiene, and face mask wearing. However, wearing face masks has not been well adopted by many citizens. While the reasons are complex, there is a general perception that the evidence to support face mask wearing is lacking, especially for the general public in a community setting. Face mask wearing can block or filter airborne virus-carrying particles through the working of colloid and interface science. This paper assesses current knowledge behind the design and functioning of face masks by reviewing the selection of materials, mask specifications, relevant laboratory tests, and respiratory virus transmission trials, with an overview of future development of reusable masks for the general public. This review highlights the effectiveness of face mask wearing in the prevention of COVID-19 infection.

18.
J Colloid Interface Sci ; 591: 106-114, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33592522

RESUMO

HYPOTHESIS: l-carnitine plays a crucial role in the cellular production of energy by transporting fatty acids into mitochondria. Acylated l-carnitines are amphiphilic and if appropriate physical properties were demonstrated, they could replace many currently used surfactants with improved biocompatibility and health benefits. EXPERIMENTS: This work evaluated the surface adsorption of lauroyl-l-carnitine (C12LC) and its aggregation behavior. The size and shape of the aggregates of C12LC surfactant were studied at different temperatures, concentrations, pH and ionic strength by dynamic light scattering (DLS) and small-angle neutron scattering (SANS). Surface tension measurements were carried out to determine the critical micellar concentration (CMC) of C12LC. Combining with the Gibbs equation, the surface excess at different concentrations could be determined. Neutron reflection (NR) was used to determine the structure of the adsorbed layer at the air/water interface with the help of isotopic contrast variations. FINDINGS: At pH 7, the limiting area per molecule (ACMC) of the zwitterionic C12LC adsorbed layer at the air/water interface was found to be 46 Å2 from surface tension and neutron reflection, smaller than the values of C12PC, C12E5, DTAB, C12C4betaine and C12C8betaine but close to that of SDS. A pronounced surface tension minimum at pH 2 at the low ionic strength was linked to a minimum value of area per molecule of about 30 Å2, indicating the competitive adsorption from traces of lauric acid produced by hydrolysis of C12LC. As the concentration increased, area per molecule reached a plateau of 37-39 Å2, indicating the dissolution of the more surface-active lauric acid into the micelles of C12LC. DLS and SANS showed that the size and shape of micelles had little response to temperature, concentration, ionic strength or pH. The SANS profiles measured under 3 isotopic contrasts could be well fitted by the core-shell model, giving a spherical core radius of 15.7 Å and a shell thickness of 10.5 Å. The decrease of pH led to more protonated carboxyl groups and more positively charged micelles, but the micellar structures remained unchanged, in spite of their stronger interaction. These features make C12LC potentially attractive as a solubilizing agent.


Assuntos
Carnitina , Tensoativos , Adsorção , Carnitina/análogos & derivados , Lauratos , Micelas , Tensão Superficial
19.
RSC Adv ; 11(25): 14957-14969, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35424047

RESUMO

A kind of high-efficiency photocatalyst of the three-dimensional flower-like TiO2/TiOF2 was synthesized by a one-step hydrothermal method. XRD, FE-SEM, EDS, HTEM, BET, XPS, PL, and UV-Vis-DRS were utilized to characterize the photocatalyst. The photocatalyst of TiO2/TiOF2 shows a narrow band gap of 2.8 eV. The generation of Ti3+ and an oxygen vacancy (Ov) in the photocatalyst are helpful to increase the absorption of visible light, and to inhibit faster charge recombination by capturing photogenerated carriers. Through the degradation of tetracycline hydrochloride (TCH) under simulated sunlight, the photocatalytic activity and stability of the synthesized samples were investigated. The results showed that the removal rate of tetracycline hydrochloride was 59% only in 0.5 h of dark reaction and 85% in 0.5 h of simulated sunlight. The removal efficiency of the photocatalyst for the adsorption and photocatalytic degradation of TCH is higher than that of the single TiO2, TiOF2, and Degussa P25. The synthesized three-dimensional flower-like TiO2/TiOF2 has great application potential in the treatment of antibiotic wastewater.

20.
RSC Adv ; 11(56): 35215-35227, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-35493161

RESUMO

Photocatalytic degradation is an eco-friendly and sustainable method for the treatment of water pollutants especially tetracycline hydrochloride (TCH). Herein, we developed F-doped H2Ti3O7-{104} nanorods with oxygen vacancies using TiOF2 as a precursor by simple alkali hydrothermal and ion-exchange methods. The phase structure, surface composition, optical properties, specific surface areas and charge separation were analysed by a series of measurements. The effects of KOH concentration on the structure and properties of H2Ti3O7 were investigated. It is confirmed that the TiOF2/H2Ti3O7 composite can be formed in low concentration KOH solution (1 mol L-1), while the H2Ti3O7 single phase can be formed in high concentration KOH solution (>3 mol L-1). The prepared F-doped H2Ti3O7-{104} nanorods provide a high specific surface area of 457 m2 g-1 and a macroporous volume of 0.69 cm3 g-1. The appropriate mesoporous structure of the photocatalyst makes TCH have a stronger affinity on its surface, which is more conducive to the subsequent photodegradation. Moreover, a synergistic mechanism of photosensitization and ligand-metal charge transfer (LMCT) in the photocatalytic degradation of TCH was proposed. In addition, the prepared F-doped H2Ti3O7-{104} nanorods showed excellent cycle stability and resistance to light corrosion. After five cycles of photodegradation, the degradation rate of TCH was only reduced from 92% to 83%. This low-cost strategy could be used for the mass production of efficient photocatalysts, which can be used for TCH clean-up in wastewater treatment.

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