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Archives of Gynecology and Obstetrics Jul 2022Bacterial vaginosis (BV) is the most common vaginal infection affecting women of childbearing age, and is associated with a substantial burden on women's physical,... (Review)
Review
Bacterial vaginosis (BV) is the most common vaginal infection affecting women of childbearing age, and is associated with a substantial burden on women's physical, emotional, sexual and social lives, as well as being linked to a number of gynaecological and obstetrical complications and adverse pregnancy outcomes. Antibiotics, such as metronidazole or clindamycin, are recommended as first-line treatment for BV, but may be associated with antibiotic resistance, high rates of recurrence and poor patient treatment satisfaction. Astodrimer sodium gel is a novel, non-antibiotic treatment for BV that is not systemically absorbed. It prevents pathogenic bacteria from adhering to the vaginal wall, and disrupts and inhibits the formation of pathogenic bacterial biofilms. Clinical cure rates of 50-57% were observed in patients with BV treated with astodrimer sodium compared with 17-21% treated with placebo (p < 0.001) in Phase 3 trials. In a separate Phase 3 trial, recurrence of BV occurred in 44% of patients treated with astodrimer sodium compared with 54% of patients who received placebo (p = 0.015). Astodrimer sodium is well tolerated, with vulvovaginal candidosis being the only treatment-related adverse event reported to occur more often than with placebo. The availability of astodrimer sodium, a well-tolerated, convenient, non-antibiotic treatment for BV, represents significant progress in the treatment of this burdensome condition.
Topics: Anti-Bacterial Agents; Bacteria; Clindamycin; Dendrimers; Female; Humans; Metronidazole; Polylysine; Pregnancy; Vaginosis, Bacterial
PubMed: 35246717
DOI: 10.1007/s00404-022-06429-z -
Protein Science : a Publication of the... Jul 2021Biomolecular condensates assembled through liquid-liquid phase separation (LLPS) of proteins and RNAs are currently recognized to play an important role in cellular...
Biomolecular condensates assembled through liquid-liquid phase separation (LLPS) of proteins and RNAs are currently recognized to play an important role in cellular organization. Their assembly depends on the formation of a network of transient, multivalent interactions between flexible scaffold biomolecules. Understanding how protein and RNA sequences determine these interactions and ultimately regulate the phase separation is an open key challenge. Recent in vitro studies have revealed that arginine and lysine residues, which are enriched in most cellular condensates, have markedly distinct propensities to drive the LLPS of protein/RNA mixtures. Here, we employ explicit-solvent atomistic molecular dynamics simulations to shed light on the microscopic origin of this difference by investigating mixtures of polyU oligonucleotides with either polyR/polyK peptides. In agreement with experiments, our simulations indicate that arginine has a higher affinity for polyU than lysine both in highly diluted conditions and in concentrated solutions with a biomolecular density comparable to cellular condensate. The analysis of intermolecular contacts suggests that this differential behavior is due to the propensity of arginine side chains to simultaneously form a higher number of specific interactions with oligonucleotides, including hydrogen bonds and stacking interactions. Our results provide a molecular description of how the multivalency of the guanidinium group enables the coordination of multiple RNA groups by a single arginine residue, thus ultimately stabilizing protein/RNA condensates.
Topics: Peptides; Poly U; Polylysine; RNA
PubMed: 33982350
DOI: 10.1002/pro.4109 -
International Journal of Biological... Dec 2023With increasing awareness on environmental protection and food safety, the development of biodegradable antimicrobial packaging materials has been paid growing emphasis....
With increasing awareness on environmental protection and food safety, the development of biodegradable antimicrobial packaging materials has been paid growing emphasis. In this work, starch/poly(butylene adipate-co-terephthalate)/ε-polylysine hydrochloride films were prepared by extrusion blowing, and five commercial organically modified nanomontmorillonites (OMMT, including DK1, DK2, DK3, DK4, and DK5) were used as reinforcing agents. Intercalated structures were formed in the nanocomposite films, especially for those with DK3 and DK4 owing to their higher hydrophobicity and larger interlayer spacing. Adding OMMT weakened hydrogen bonds and the gelatinization/plasticization degree of starch. Morphology analysis revealed that the agglomeration of OMMT occurred in the films, but the film containing DK3 still showed a relatively homogeneous microstructure. Loading OMMT enhanced the strength, deformation resistance, thermal stability, surface hydrophobicity, but decreased barrier properties and water sensitivity of the films. Antimicrobial activity showed that the OMMT and ε-polylysine hydrochloride possessed a synergistic effect against Staphylococcus aureus and Escherichia coli. The maximum inhibition rate was observed in that with DK4, approaching 100 %. Findings supported the application of commercial OMMT in manufacturing biodegradable antimicrobial blown films.
Topics: Polyesters; Polylysine; Starch; Anti-Infective Agents; Adipates
PubMed: 37652334
DOI: 10.1016/j.ijbiomac.2023.126609 -
Biochemical and Biophysical Research... Apr 2023Chitooligosaccharides can be combined with amino acids or polypeptide to form Maillard reaction products (MRPs) with the antibacterial characteristics through Maillard...
Chitooligosaccharides can be combined with amino acids or polypeptide to form Maillard reaction products (MRPs) with the antibacterial characteristics through Maillard reaction. This research aims to clarify the structure, antimicrobial effect and mechanism against Shewanella putrefaciens (S. putrefaciens) of ε-polylysine and chitooligosaccharides Maillard reaction products (LC-MRPs). The results of intrinsic fluorescence (IF) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction, proton nuclear magnetic resonance (H NMR) spectra and scanning electron microscope (SEM) indicated Maillard reaction occurred between ε-polylysine and chitooligosaccharides. The observation of confocal laser scanning microscopy (CLSM), SEM and growth curves of S. putrefaciens evidenced that LC-MRPs have the strongest antibacterial effects. The leakage of alkaline phosphatase (AKP) and lactate dehydrogenase (LDH) implied that LC-MRPs sabotaged bacterial barrier (cell wall and cell membrane). The changes in content of nucleic acids, reactive oxygen species (ROS) level, lipid peroxidation content (LPO), succinate dehydrogenase (SDH) activity and adenosine triphosphate (ATP) content showed LC-MRPs will affect bacterial genetic gene transcription, material and energy metabolism. Therefore, the LC-MRPs were effective antibacterial agents to inhibit S. putrefaciens, which will help to preserve food with S. putrefaciens as the main spoilage bacteria.
Topics: Polylysine; Spectroscopy, Fourier Transform Infrared; Anti-Infective Agents; Anti-Bacterial Agents; Maillard Reaction; Glycation End Products, Advanced
PubMed: 36773337
DOI: 10.1016/j.bbrc.2023.01.078 -
Macromolecular Bioscience Apr 2023Endothelialization of the aneurysmal neck is essential for aneurysm healing after endovascular treatment. Mesenchymal stem cell (MSC)-seeded stents can promote aneurysm...
Endothelialization of the aneurysmal neck is essential for aneurysm healing after endovascular treatment. Mesenchymal stem cell (MSC)-seeded stents can promote aneurysm repair. The biological effects of coated and uncoated nitinol intracranial stents seeded with MSCs on vascular cells and macrophage proliferation and inflammation are investigated. Two stent coatings that exert pro-aggregation effects on MSCs via different mechanisms are examined: gelatin/polylysine (G/PLL), which enhances cell adhesion, and silk fibroin/SDF-1α (SF/SDF-1α), which enhances chemotaxis. The aim is to explore the feasibility of MSC-seeded coated stents in the treatment of intracranial aneurysms. The G/PLL coating provides the highest cytocompatibility and blood compatibility substrate for MSCs and vascular cells and promotes cell adhesion and proliferation. Moreover, it enhances MSC secretion and regulation of vascular cell and macrophage proliferation and chemotaxis. Although the SF/SDF-1α coating promotes MSC secretion and vascular cell chemotaxis, it induces a greater degree of macrophage proliferation, chemotaxis, and secretion of pro-inflammatory factors. MSC-seeded stents coated with G/PLL may benefit stent surface endothelialization and reduce the inflammatory response after endovascular treatment of intracranial aneurysm. These effects may improve aneurysm healing and increase the cure rate.
Topics: Humans; Chemokine CXCL12; Fibroins; Gelatin; Polylysine; Stents; Intracranial Aneurysm; Mesenchymal Stem Cells
PubMed: 36541928
DOI: 10.1002/mabi.202200402 -
The Journal of Clinical Investigation Feb 2022BACKGROUNDLong-term prognosis of WHO grade II low-grade gliomas (LGGs) is poor, with a high risk of recurrence and malignant transformation into high-grade gliomas.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUNDLong-term prognosis of WHO grade II low-grade gliomas (LGGs) is poor, with a high risk of recurrence and malignant transformation into high-grade gliomas. Given the relatively intact immune system of patients with LGGs and the slow tumor growth rate, vaccines are an attractive treatment strategy.METHODSWe conducted a pilot study to evaluate the safety and immunological effects of vaccination with GBM6-AD, lysate of an allogeneic glioblastoma stem cell line, with poly-ICLC in patients with LGGs. Patients were randomized to receive the vaccines before surgery (arm 1) or not (arm 2) and all patients received adjuvant vaccines. Coprimary outcomes were to evaluate safety and immune response in the tumor.RESULTSA total of 17 eligible patients were enrolled - 9 in arm 1 and 8 in arm 2. This regimen was well tolerated with no regimen-limiting toxicity. Neoadjuvant vaccination induced upregulation of type-1 cytokines and chemokines and increased activated CD8+ T cells in peripheral blood. Single-cell RNA/T cell receptor sequencing detected CD8+ T cell clones that expanded with effector phenotype and migrated into the tumor microenvironment (TME) in response to neoadjuvant vaccination. Mass cytometric analyses detected increased tissue resident-like CD8+ T cells with effector memory phenotype in the TME after the neoadjuvant vaccination.CONCLUSIONThe regimen induced effector CD8+ T cell response in peripheral blood and enabled vaccine-reactive CD8+ T cells to migrate into the TME. Further refinements of the regimen may have to be integrated into future strategies.TRIAL REGISTRATIONClinicalTrials.gov NCT02549833.FUNDINGNIH (1R35NS105068, 1R21CA233856), Dabbiere Foundation, Parker Institute for Cancer Immunotherapy, and Daiichi Sankyo Foundation of Life Science.
Topics: Adult; Aged; CD8-Positive T-Lymphocytes; Cancer Vaccines; Carboxymethylcellulose Sodium; Female; Glioma; Humans; Male; Middle Aged; Neoadjuvant Therapy; Poly I-C; Polylysine; Tumor Microenvironment; Vaccination
PubMed: 34882581
DOI: 10.1172/JCI151239 -
International Journal of Biological... Dec 2022Cutaneous wound management remains a major concern due to uncontrolled inflammation and bacterial infection in clinical care. A desirable hydrogel dressing with...
Cutaneous wound management remains a major concern due to uncontrolled inflammation and bacterial infection in clinical care. A desirable hydrogel dressing with antibacterial and antioxidative properties can drive wound healing by inhibiting infection and inflammation. Herein, a multifunctional hydrogel based on polylysine-graft-cysteine (EPL-SH)/oxidized dextran (ODex) was fabricated for promoting skin tissue regeneration. The engineered hydrogel possessed versatile properties including tunable gelation time (60-300 s), typical rheological behavior, suitable swelling and degradation progress, injectable and self-healing ability. The unique hydrogels also displayed promising tissue adhesiveness, high cell affinity, excellent antioxidant and antimicrobial activity. Furthermore, the in vivo full-thickness skin defect experiment demonstrated the simple-to-implement injectable hydrogels could significantly promoting wound healing by improving the collagen deposition and angiogenesis. The manufacture of our multifunctional hydrogels dressing affords a new strategy for improving efficacy of cutaneous wound treatment.
Topics: Hydrogels; Dextrans; Polylysine; Wound Healing; Anti-Bacterial Agents; Antioxidants
PubMed: 36375676
DOI: 10.1016/j.ijbiomac.2022.11.065 -
International Journal of Biological... Nov 2023The ε-polylysine (ε-PL) is a food-grade antimicrobial substance. The cationic ε-PL molecules may interact with anionic components of food matrix causing turbidity,...
The ε-polylysine (ε-PL) is a food-grade antimicrobial substance. The cationic ε-PL molecules may interact with anionic components of food matrix causing turbidity, sedimentation, and hampering the antimicrobial activity. Herein, sodium alginate (SA) was used as wall material to encapsulate ε-PL, thereby to synthesize ε-PL-SA nanoparticles (ε-PL-SA-NPs). Monosaccharide composition and molecular weight of SA were characterized. The synthetic scheme is optimized and physicochemical characteristics and antimicrobial potential was investigated. Findings indicate that SA primarily consisted of mannuronic acid (95.25 %), weight average molecular weight (Mw) of SA was 176.464 kDa, and the molecular configuration of SA was irregular line clusters. The encapsulation efficiency (EE) of ε-PL in ε-PL-SA-NPs made under optimum strategy (at pH 6.0, mass ratio of ε-PL to SA is 0.14, and SA concentration is 6 mg/mL) is about 99.74 %. The particle size of ε-PL-SA-NPs is ∼541.86 nm. The SEM image showed that the ε-PL-SA-NPs had a nearly spherical morphology. Zeta-potential and FTIR data reveal the interaction between ε-PL and SA was electrostatic and the hydrogen bonding. Agar diffusion assay exhibit that ε-PL-SA-NPs had antimicrobial activity against Escherichia coli and Staphylococcus aureus. The salmon preservation experiments reveal sustained antimicrobial efficacy of ε-PL-SA-NPs.
Topics: Alginates; Polylysine; Nanoparticles; Particle Size; Anti-Infective Agents; Staphylococcus aureus; Molecular Weight; Escherichia coli; Anti-Bacterial Agents; Microbial Sensitivity Tests; Drug Carriers
PubMed: 37595718
DOI: 10.1016/j.ijbiomac.2023.126329 -
Viruses Jan 2020The human OAS1 (hOAS1) gene produces multiple possible isoforms due to alternative splicing events and sequence variation among individuals, some of which affect...
The human OAS1 (hOAS1) gene produces multiple possible isoforms due to alternative splicing events and sequence variation among individuals, some of which affect splicing. The unique C-terminal sequences of the hOAS1 isoforms could differentially affect synthetase activity, protein stability, protein partner interactions and/or cellular localization. Recombinant p41, p42, p44, p46, p48, p49 and p52 hOAS1 isoform proteins expressed in bacteria were each able to synthesize trimer and higher order 2'-5' linked oligoadenylates in vitro in response to poly(I:C). The p42, p44, p46, p48 and p52 isoform proteins were each able to induce RNase-mediated rRNA cleavage in response to poly(I:C) when overexpressed in HEK293 cells. The expressed levels of the p42 and p46 isoform proteins were higher than those of the other isoforms, suggesting increased stability in mammalian cells. In a yeast two-hybrid screen, Fibrillin1 (FBN1) was identified as a binding partner for hOAS1 p42 isoform, and Supervillin (SVIL) as a binding partner for the p44 isoform. The p44-SVIL interaction was supported by co-immunoprecipitation data from mammalian cells. The data suggest that the unique C-terminal regions of hOAS1 isoforms may mediate the recruitment of different partners, alternative functional capacities and/or different cellular localization.
Topics: 2',5'-Oligoadenylate Synthetase; Alternative Splicing; Cloning, Molecular; Escherichia coli; Fibrillin-1; Gene Expression; HEK293 Cells; Humans; Membrane Proteins; Microfilament Proteins; Poly I-C; Polylysine; Protein Isoforms; Recombinant Proteins
PubMed: 32013110
DOI: 10.3390/v12020152 -
Seminars in Immunology Jun 2020Immunotherapies have become the first line of treatment for many cancer types. Unfortunately, only a small fraction of patients benefits from these therapies. This low... (Review)
Review
Immunotherapies have become the first line of treatment for many cancer types. Unfortunately, only a small fraction of patients benefits from these therapies. This low rate of success can be attributed to 3 main barriers: 1) low frequency of anti-tumor specific T cells; 2) lack of infiltration of the anti-tumor specific T cells into the tumor parenchyma and 3) accumulation of highly suppressive cells in the tumor mass that inhibit the effector function of the anti-tumor specific T cells. Thus, the identification of immunomodulators that can increase the frequency and/or the infiltration of antitumor specific T cells while reducing the suppressive capacity of the tumor microenvironment is necessary to ensure the effectiveness of T cell immunotherapies. In this review, we discuss the potential of poly-ICLC as a multi-functional immune modulator for treating cancer and its impact on the 3 above mentioned barriers. We describe the unique capacity of poly-ICLC in stimulating 2 separate pattern recognition receptors, TLR3 and cytosolic MDA5 and the consequences of these activations on cytokines and chemokines production. We emphasize the role of poly-ICLC as an adjuvant in the setting of peptide-based cancer vaccines and in situ tumor vaccination by mimicking natural immune responses to infections. Finally, we summarize the impact of poly-ICLC in enhancing T infiltration into the tumor parenchyma and address the implication of this finding in the clinic.
Topics: Animals; Antineoplastic Agents; Carboxymethylcellulose Sodium; Cytokines; Humans; Immunity, Innate; Immunologic Factors; Immunomodulation; Interferon-Induced Helicase, IFIH1; Lymphocytes, Tumor-Infiltrating; Neoplasms; Poly I-C; Polylysine; Receptors, Pattern Recognition; Toll-Like Receptor 3
PubMed: 33011064
DOI: 10.1016/j.smim.2020.101414