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Biomolecules Aug 2023The widespread incidence of antimicrobial resistance necessitates the discovery of new classes of antimicrobials as well as adjuvant molecules that can restore the...
The widespread incidence of antimicrobial resistance necessitates the discovery of new classes of antimicrobials as well as adjuvant molecules that can restore the action of ineffective antibiotics. Herein, we report the synthesis of a new class of indole-3-acetamido-polyamine conjugates that were evaluated for antimicrobial activities against a panel of bacteria and two fungi, and for the ability to enhance the action of doxycycline against and erythromycin against . Compounds , , , , , , , , and exhibited strong growth inhibition of methicillin-resistant (MRSA) and , with minimum inhibitory concentrations (MIC) typically less than 0.2 µM. Four analogues, including a 5-bromo and three 5-methoxyls - also exhibited intrinsic activity towards . Antibiotic kill curve analysis of identified it to be a bactericide. While only one derivative was found to (weakly) enhance the action of erythromycin against , three examples, including , were found to be strong enhancers of the antibiotic action of doxycycline against . Collectively, these results highlight the promising potential of α,ω-disubstituted indole-3-acetamido polyamine conjugates as antimicrobials and antibiotic adjuvants.
Topics: Anti-Bacterial Agents; Doxycycline; Escherichia coli; Methicillin-Resistant Staphylococcus aureus; Anti-Infective Agents; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Erythromycin; Fatty Acids, Omega-3; Indoles; Polyamines; Pseudomonas aeruginosa
PubMed: 37627291
DOI: 10.3390/biom13081226 -
Upsala Journal of Medical Sciences May 2020The field of assisted reproductive technology is shaped and changed constantly by advances in science and cutting-edge innovations. In a quest to maximise outcomes,... (Review)
Review
The field of assisted reproductive technology is shaped and changed constantly by advances in science and cutting-edge innovations. In a quest to maximise outcomes, add-on interventions are often adopted and utilised prematurely while the principles of evidence-based medicine seem to be less strictly adhered to. In this review we will attempt to summarise the latest evidence about some of the adjuvants.
Topics: Adjuvants, Pharmaceutic; Evidence-Based Medicine; Fertilization in Vitro; Humans; Patient-Centered Care
PubMed: 32378442
DOI: 10.1080/03009734.2020.1751751 -
ChemistryOpen Apr 2023As vaccine adjuvants, polyacrylate materials can induce a specific immune response in the body and have been widely studied in recent years due to their advantages, such...
As vaccine adjuvants, polyacrylate materials can induce a specific immune response in the body and have been widely studied in recent years due to their advantages, such as their safety, effectiveness, and low required dosage. In this study, a series of polyacrylates with hydrophobic physical crosslinking and chemical crosslinking were prepared using precipitation polymerization, and their structures were characterized by nuclear magnetic resonance spectroscopy and Fourier-transform infrared spectroscopy. The optimal reaction conditions were determined according to the effect of reaction time, azodiisobutyronitrile, Span 60, allyl pentaerythritol, and octadecyl methacrylate (OMA) contents on the viscosity of the polyacrylate microgel, combined with the effects of allyl pentaerythritol and OMA contents on the subcutaneous immune safety of the polyacrylate microgel in BALB/c mice. The polyacrylate microgels with different OMA contents showed good biological safety. In addition, in vivo immunity experiments were carried out in mice to analyze the adjuvant properties of ovalbumin as a model antigen. Based on the titer results of the IgG1 and IgG2a antibodies, with 1 wt % OMA content, the polyacrylate microgel vaccine could optimally induce the body to produce an immune response type dominated by Th2-type humoral immune response and supplemented by Th1-type cellular immune response.
Topics: Animals; Mice; Microgels; Ovalbumin; Th1 Cells; Th2 Cells; Adjuvants, Immunologic; Antigens; Adjuvants, Pharmaceutic
PubMed: 37009889
DOI: 10.1002/open.202200246 -
Biomedicine & Pharmacotherapy =... Sep 2022Glioma is the most common primary malignant tumor of the central nervous system. Although surgical treatment combined with radiotherapy, chemotherapy, and immunotherapy... (Review)
Review
Glioma is the most common primary malignant tumor of the central nervous system. Although surgical treatment combined with radiotherapy, chemotherapy, and immunotherapy are commonly used for glioma treatment, the prognosis of glioma is still unsatisfactory. The poor effect of glioma treatment could be due to the blocking effect of blood-brain barrier (BBB) on most drugs and the multidrug resistance in tumor cells. In recent years, preclinical trials have shown that low-intensity ultrasound (LIUS) can reversibly open the BBB, inhibit the proliferation of tumor cells, and improve the delivery of drugs to brain tissue. This technology has also recently been used in clinical trials, and achieved encouraging preliminary results. In this review, the existing research results, the effect of LIUS on the adjuvant therapy of glioma under safe conditions, and the physical and biological mechanisms have been discussed. This review aims to show the potential and prospect of LIUS technique in the clinical treatment of glioma.
Topics: Adjuvants, Pharmaceutic; Blood-Brain Barrier; Brain Neoplasms; Combined Modality Therapy; Glioma; Humans; Immunotherapy
PubMed: 36036428
DOI: 10.1016/j.biopha.2022.113394 -
Journal of Pain and Symptom Management Nov 1994There has been long-standing debate regarding whether benzodiazepines possess analgesic properties that are independent of their effects on mood and alertness. A careful... (Review)
Review
There has been long-standing debate regarding whether benzodiazepines possess analgesic properties that are independent of their effects on mood and alertness. A careful review of the literature reveals insufficient evidence to support the contention that the benzodiazepines have meaningful analgesic properties in most clinical circumstances. Treatment with the benzodiazepines may reduce complaints of pain, but this seems to be an indirect effect related to their psychotropic properties, such as alleviation of anxiety and, in selected cases, depression. In the absence of definitive data, clinical experience suggests a potential role for treatment with benzodiazepines for acute muscle spasm, concomitant chronic pain and anxiety, and lancinating neropathic pain, in which case clonazepam and alprazolam may be the agents of choice. They should probably not be considered as first-line choices even for the above indications, since potential benefits must be considered in the context of potential for the development of cognitive impairment, physical and psychological dependence, worsening depression, overdose, and other side effects.
Topics: Adjuvants, Pharmaceutic; Analgesics; Benzodiazepines; Clinical Trials as Topic; Humans; Palliative Care
PubMed: 7531735
DOI: 10.1016/0885-3924(94)90112-0 -
Expert Opinion on Investigational Drugs Nov 2013β-blockers are a class of drugs that are widely used in treating cardiac, respiratory and other ailments. They act by blocking β-adrenergic receptor-mediated...
β-blockers are a class of drugs that are widely used in treating cardiac, respiratory and other ailments. They act by blocking β-adrenergic receptor-mediated signaling. Studies in various cancers have shown that patients taking a β-blocker have higher survival and lower recurrence and metastasis rates. This is supported by several preclinical and in vitro studies showing that adrenergic activation modulates apoptosis, promotes angiogenesis and other cancer hallmarks, and these effects can be abrogated by β-blockers. These studies provide a rationale for the use of β-blockers as adjuvants with cancer chemotherapy. However, all published studies so far are retrospective and most do not take into account the specific β-blocker used or address which is most likely to benefit cancer patients. The published epidemiological studies are correlative and have not examined the adrenergic receptor status of the tumors. Knowledge of the β-adrenergic receptor status of tumor cells is essential in choosing the best β-blocker for adjuvant therapy. A comprehensive, prospective study is necessary to definitively prove the utility of using β-blockers with chemotherapy and to identify the specific β-blocker most likely to benefit patients with cancer.
Topics: Adjuvants, Pharmaceutic; Adrenergic beta-Antagonists; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Humans; Neoplasms
PubMed: 23919278
DOI: 10.1517/13543784.2013.825250 -
The Annals of Pharmacotherapy Nov 2023The objective of this study was to review the effectiveness and safety of COVID-19 vaccinations in the pediatric population. (Review)
Review
OBJECTIVE
The objective of this study was to review the effectiveness and safety of COVID-19 vaccinations in the pediatric population.
DATA SOURCES
PubMed/Medline (September 2020 to December 2022), the Centers for Disease Control and Prevention, and Food and Drug Administration (FDA) websites.
STUDY SELECTION AND DATA EXTRACTION
Publications regarding the safety and efficacy of COVID-19 vaccinations in children were included.
DATA SYNTHESIS
Vaccines authorized for use in children include two monovalent mRNA vaccines (≥6 months old) and one monovalent protein subunit adjuvant vaccine (adolescents only). Omicron-specific mRNA bivalent boosters are authorized for children ≥6 months old. Studies after monovalent vaccine authorization illustrated efficacy in children >5 to 6 years of age, specifically decreased severe COVID-19 (including mortality) and multisystem inflammatory response syndrome occurrence (including during Omicron predominance). Available data for children <5 to 6 years suggests efficacy, although data are limited. Monovalent vaccine efficacy against Omicron infections may wane as early as 2 months, but protection against severe disease complications may last longer, and bivalent Omicron boosters are anticipated to increase effectiveness. Myocarditis/pericarditis is a safety concern associated with the COVID-19 vaccinations but occurs less frequently then COVID-19 complications and thus the benefit outweighs the risks.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Caregivers seek information from health care professionals regarding vaccine safety and efficacy. Pharmacists can use the objective information in this review to educate caregivers and effectively administer COVID-19 vaccines to patients.
CONCLUSIONS
There is sufficient and continually growing safety and efficacy data available to recommend COVID-19 vaccinations for children ≥6 months of age.
Topics: Child; United States; Adolescent; Humans; Infant; COVID-19 Vaccines; COVID-19; Vaccination; Adjuvants, Pharmaceutic; Health Personnel
PubMed: 36847285
DOI: 10.1177/10600280231156625 -
Frontiers in Immunology 2022Recently, bacterial components were shown to enhance immune responses by shifting immune cell metabolism towards glycolysis and lactic acid production, also known as the...
BACKGROUND
Recently, bacterial components were shown to enhance immune responses by shifting immune cell metabolism towards glycolysis and lactic acid production, also known as the Warburg Effect. Currently, the effect of allergen products for immunotherapy (AIT) and commercial vaccines on immune cell metabolism is mostly unknown.
OBJECTIVE
To investigate the effect of AIT products (adjuvanted with either MPLA or Alum) on myeloid dendritic cell (mDC) metabolism and activation.
METHODS
Bone marrow-derived mDCs were stimulated with five allergoid-based AIT products (one adjuvanted with MPLA, four adjuvanted with Alum) and two MPLA-adjuvanted vaccines and analyzed for their metabolic activation, expression of cell surface markers, and cytokine secretion by ELISA. mDCs were pre-incubated with either immunological or metabolic inhibitors or cultured in glucose- or glutamine-free culture media and subsequently stimulated with the MPLA-containing AIT product (AIT product 1). mDCs were co-cultured with allergen-specific CD4+ T cells to investigate the contribution of metabolic pathways to the T cell priming capacity of mDCs stimulated with AIT product 1.
RESULTS
Both the MPLA-containing AIT product 1 and commercial vaccines, but not the Alum-adjuvanted AIT products, activated Warburg metabolism and TNF-α secretion in mDCs. Further experiments focused on AIT product 1. Metabolic analysis showed that AIT product 1 increased glycolytic activity while also inducing the secretion of IL-1β, IL-10, IL-12, and TNF-α. Both rapamycin (mTOR-inhibitor) and SP600125 (SAP/JNK MAPK-inhibitor) dose-dependently suppressed the AIT product 1-induced Warburg Effect, glucose consumption, IL-10-, and TNF-α secretion. Moreover, both glucose- and glutamine deficiency suppressed secretion of all investigated cytokines (IL-1β, IL-10, and TNF-α). Glucose metabolism in mDCs was also critical for the (Th1-biased) T cell priming capacity of AIT product 1-stimulated mDCs, as inhibition of mTOR signaling abrogated their ability to induce Th1-responses.
CONCLUSION
The AIT product and commercial vaccines containing the adjuvant MPLA were shown to modulate the induction of immune responses by changing the metabolic state of mDCs. Better understanding the mechanisms underlying the interactions between cell metabolism and immune responses will allow us to further improve vaccine development and AIT.
Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Allergens; Dendritic Cells; Glucose; Immunologic Factors; Immunotherapy; Interleukin-10; TOR Serine-Threonine Kinases; Tumor Necrosis Factor-alpha; Vaccines
PubMed: 36059475
DOI: 10.3389/fimmu.2022.916491 -
Frontiers in Immunology 2024Type I hypersensitivity, or so-called type I allergy, is caused by Th2-mediated immune responses directed against otherwise harmless environmental antigens. Currently,... (Review)
Review
Type I hypersensitivity, or so-called type I allergy, is caused by Th2-mediated immune responses directed against otherwise harmless environmental antigens. Currently, allergen-specific immunotherapy (AIT) is the only disease-modifying treatment with the potential to re-establish clinical tolerance towards the corresponding allergen(s). However, conventional AIT has certain drawbacks, including long treatment durations, the risk of inducing allergic side effects, and the fact that allergens by themselves have a rather low immunogenicity. To improve AIT, adjuvants can be a powerful tool not only to increase the immunogenicity of co-applied allergens but also to induce the desired immune activation, such as promoting allergen-specific Th1- or regulatory responses. This review summarizes the knowledge on adjuvants currently approved for use in human AIT: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine, and MPLA, as well as novel adjuvants that have been studied in recent years: oil-in-water emulsions, virus-like particles, viral components, carbohydrate-based adjuvants (QS-21, glucans, and mannan) and TLR-ligands (flagellin and CpG-ODN). The investigated adjuvants show distinct properties, such as prolonging allergen release at the injection site, inducing allergen-specific IgG production while also reducing IgE levels, as well as promoting differentiation and activation of different immune cells. In the future, better understanding of the immunological mechanisms underlying the effects of these adjuvants in clinical settings may help us to improve AIT.
Topics: Humans; Desensitization, Immunologic; Hypersensitivity; Adjuvants, Immunologic; Allergens; Aluminum Hydroxide; Adjuvants, Pharmaceutic
PubMed: 38464539
DOI: 10.3389/fimmu.2024.1348305 -
Journal of Controlled Release :... Mar 2023Self-adjuvanting protein vaccines have been proved to be highly immunogenic with efficient codelivery of adjuvant and antigen. Current protein vaccines with built-in...
Self-adjuvanting protein vaccines have been proved to be highly immunogenic with efficient codelivery of adjuvant and antigen. Current protein vaccines with built-in adjuvants are all modified at the peptide backbone of antigen protein, which could not achieve minor epitope interference and adjuvant multivalency at the same time. Herein, we developed a new conjugate strategy to construct effective adjuvant-protein vaccine with adjuvant cluster effect and minimal epitope interference. The toll-like receptor 7 agonist (TLR7a) is covalently conjugated on the terminal sialoglycans of SARS-CoV-2-S1 protein, leading to intracellular release of the small-molecule stimulators with greatly reduced risks of systemic toxicity. The resulting TLR7a-S1 conjugate elicited strong activation of immune cells in vitro, and potent antibody and cellular responses with a significantly enhanced Th1-bias in vivo. TLR7a-S1-induced antibody also effectively cross-neutralized all variants of concern. This sialoglycoconjugation approach to construct protein conjugate vaccines will have more applications to combat SARS-CoV-2 and other diseases.
Topics: Humans; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Adjuvants, Immunologic; Antigens; Adjuvants, Pharmaceutic; Epitopes
PubMed: 36716860
DOI: 10.1016/j.jconrel.2023.01.062