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Frontiers in Immunology 2022Adjuvants are important vaccine components, composed of a variety of chemical and biological materials that enhance the vaccine antigen-specific immune responses by...
Adjuvants are important vaccine components, composed of a variety of chemical and biological materials that enhance the vaccine antigen-specific immune responses by stimulating the innate immune cells in both direct and indirect manners to produce a variety cytokines, chemokines, and growth factors. It has been developed by empirical methods for decades and considered difficult to choose a single screening method for an ideal vaccine adjuvant, due to their diverse biochemical characteristics, complex mechanisms of, and species specificity for their adjuvanticity. We therefore established a robust adjuvant screening strategy by combining multiparametric analysis of adjuvanticity and immunological profiles (such as cytokines, chemokines, and growth factor secretion) of various library compounds derived from hot-water extracts of herbal medicines, together with their diverse distribution of nano-sized physical particle properties with a machine learning algorithm. By combining multiparametric analysis with a machine learning algorithm such as rCCA, sparse-PLS, and DIABLO, we identified that human G-CSF and mouse RANTES, produced upon adjuvant stimulation , are the most robust biological parameters that can predict the adjuvanticity of various library compounds. Notably, we revealed a certain nano-sized particle population that functioned as an independent negative parameter to adjuvanticity. Finally, we proved that the two-step strategy pairing the negative and positive parameters significantly improved the efficacy of screening and a screening strategy applying principal component analysis using the identified parameters. These novel parameters we identified for adjuvant screening by machine learning with multiple biological and physical parameters may provide new insights into the future development of effective and safe adjuvants for human use.
Topics: Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Adjuvants, Vaccine; Animals; Cytokines; Herbal Medicine; Machine Learning; Mice; Vaccines
PubMed: 35663999
DOI: 10.3389/fimmu.2022.847616 -
Clinical Biochemistry Sep 2014The experience of chronic pain is one of the commonest reasons individuals seek medical attention, making the management of chronic pain a major issue in clinical... (Review)
Review
OBJECTIVE
The experience of chronic pain is one of the commonest reasons individuals seek medical attention, making the management of chronic pain a major issue in clinical practice. Drug metabolism and responses are affected by many factors, with genetic variations offering only a partial explanation of an individual's response. There is a paucity of evidence for the benefits of pharmacogenetic testing in the context of pain management.
DESIGN AND METHODS
We reviewed the literature between 2000 and 2013, and references cited therein, using various keywords related to pain management, pharmacology and pharmacogenetics.
RESULTS
Opioids continue to be the mainstay of chronic pain management. Several non-opioid based therapies, such as treatment with cannabinoids, gene therapy and epigenetic-based approaches are now available for these patients. Adjuvant therapies with antidepressants, benzodiazepines or anticonvulsants can also be useful in managing pain. Currently, laboratory monitoring of pain management patients, if performed, is largely through urine drug measurements.
CONCLUSIONS
Drug half-life calculations can be used as functional markers of the cumulative effect of pharmacogenetics and drug-drug interactions. Assessment of half-life and therapeutic effects may be more useful than genetic testing in preventing adverse drug reactions to pain medications, while ensuring effective analgesia. Definitive, mass spectrometry-based methods, capable of measuring parent drug and metabolite levels, are the most useful assays for this purpose. Urine drug measurements do not necessarily correlate with serum drug concentrations or therapeutic effects. Therefore, they are limited in their use in monitoring efficacy and toxicity.
Topics: Adjuvants, Pharmaceutic; Analgesics, Opioid; Chronic Pain; Drug Interactions; Humans; Pain Management; Pharmacogenetics
PubMed: 24912048
DOI: 10.1016/j.clinbiochem.2014.05.065 -
Supportive Care in Cancer : Official... Apr 2023Adjuvant endocrine therapy reduces the recurrence and mortality of early hormone receptor-positive breast cancer in both pre- and postmenopausal women. The aim of this...
PURPOSE
Adjuvant endocrine therapy reduces the recurrence and mortality of early hormone receptor-positive breast cancer in both pre- and postmenopausal women. The aim of this study was to investigate adjuvant tamoxifen adherence and associated factors in breast cancer survivors.
METHODS
This descriptive, prospective study was conducted in 2019-2020 with the participation of 531 women who survived breast cancer and were under follow-up at the Senology Institute of a hospital in Istanbul. Inclusion criteria were having completed treatment for early hormone receptor-positive breast cancer, being prescribed tamoxifen, and being 18 years or older. Data were collected using a patient information form and the Morisky Medication Adherence Scale-8 (MMAS-8).
RESULTS
The mean age of the participants was 44.9 ± 6.5 years, and the mean duration of tamoxifen use was 834.4 ± 685.7 days. The women's mean MMAS-8 score was 6.86 ± 1.39. Medication adherence was significantly positively correlated with current age (p = 0.006) and age at diagnosis (p = 0.002). There was a statistically significant difference between tamoxifen adherence according to participants' employment status (p = 0.028), chronic disease status (p = 0.018), loss of libido (p = 0.012), treatment-related changes in mood changes (p = 0.004), and having negative effects affecting daily life (p < 0.001).
CONCLUSION
Overall, breast cancer survivors in this study reported moderate adherence to tamoxifen. The women's individual characteristics and the adverse effects of treatment influenced medication adherence. Healthcare professionals can help increase adherence to this treatment, which reduces the risk of mortality, by explaining the importance of the medication, identifying and eliminating barriers to adherence, and informing women about evidence-based interventions to increase medication compliance.
Topics: Female; Humans; Adult; Middle Aged; Tamoxifen; Breast Neoplasms; Cancer Survivors; Antineoplastic Agents, Hormonal; Prospective Studies; Chemotherapy, Adjuvant; Medication Adherence; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Aromatase Inhibitors
PubMed: 37079089
DOI: 10.1007/s00520-023-07742-2 -
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 -
Frontiers in Immunology 2023African swine fever (ASF) is an infectious disease caused by African swine fever virus (ASFV) that is highly contagious and has an extremely high mortality rate...
African swine fever (ASF) is an infectious disease caused by African swine fever virus (ASFV) that is highly contagious and has an extremely high mortality rate (infected by virulent strains) among domestic and wild pigs, causing huge economic losses to the pig industry globally. In this study, SDS-PAGE gel bands hybridized with ASFV whole virus protein combined with ASFV-convalescent and ASFV-positive pig serum were identified by mass spectrometry. Six antigens were detected by positive serum reaction bands, and eight antigens were detected in ASFV-convalescent serum. In combination with previous literature reports and proteins corresponding to MHC-II presenting peptides screened from ASFV-positive pig urine conducted in our lab, seven candidate antigens, including KP177R (p22), K78R (p10), CP204L (p30), E183L (p54), B602L (B602L), EP402R-N (CD2V-N) and F317L (F317L), were selected. Subunit-Group 1 was prepared by mixing above-mentioned seven ASFV recombinant proteins with MONTANIDETM1313 VG N mucosal adjuvant and immunizing pigs intranasally and intramuscularly. Subunit-Group 2 was prepared by mixing four ASFV recombinant proteins (p22, p54, CD2V-N1, B602L) with Montanide ISA 51 VG adjuvant and immunizing pigs by intramuscular injection. Anticoagulated whole blood, serum, and oral fluid were collected during immunization for flow cytometry, serum IgG as well as secretory sIgA antibody secretion, and cytokine expression testing to conduct a comprehensive immunogenicity assessment. Both immunogen groups can effectively stimulate the host to produce ideal humoral, mucosal, and cellular immune responses, providing a theoretical basis for subsequent functional studies, such as immunogens challenge protection and elucidation of the pathogenic mechanism of ASFV.
Topics: Animals; Swine; African Swine Fever Virus; African Swine Fever; Vaccination; Immunization; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Histocompatibility Antigens Class II; Immunity, Cellular
PubMed: 37720232
DOI: 10.3389/fimmu.2023.1200297 -
Phytomedicine : International Journal... Feb 2024Extensive investigation has been undertaken about the utilization of saponin adjuvants in vaccines intended for veterinary and human applications. AB4 is the main...
BACKGROUND
Extensive investigation has been undertaken about the utilization of saponin adjuvants in vaccines intended for veterinary and human applications. AB4 is the main constituent of the traditional Chinese medicine, Pulsatilla chinensis (Bunge) Regel, and has immunomodulatory activity. However, there is a paucity of reports on AB4 as a potential adjuvant.
PURPOSE
The objective of this work was to clarify the adjuvant role of AB4 and the molecular mechanisms that underlie its immunomodulatory actions.
STUDY DESIGN AND METHODS
The immunomodulatory effects of AB4 were investigated using network pharmacological analyses. These effects were validated by evaluating the developmental status of the immune organs and by using the following techniques: ELISA for the quantification of serum-specific antibodies to determine immune-related cytokine levels; the MTS method for the assessment of proliferative activity of splenic lymphocytes; flow cytometry to analyze lymphocyte and dendritic cell activation status; and western blotting for mechanistic analysis at the protein level.
RESULTS
The network pharmacological analysis predicted a total of 52 targets and 12 pathways for AB4 to exert immunomodulatory effects. In a mouse model with immunity to OVA, the introduction of AB4 resulted in the enhancement of immunological organ growth and maturation, elevation of blood antibodies targeting OVA, and amplification of the production of cytokines associated with Th1 and Th2 immune responses. Additionally, the administration of AB4 resulted in a notable augmentation of lymphocyte proliferation and an elevation in the CD4+/CD8+ T lymphocyte ratios. Furthermore, the administration of AB4 enhanced the maturation process of DCs in the draining LNs and increased the production of co-stimulatory factors and MHC II molecules. AB4 induces the upregulation of TLR4 and IKK proteins, as well as the phosphorylation of NF-κB p65 protein within the TLR4/NF-κB signaling cascade, while concurrently suppressing the expression of IκBα protein.
CONCLUSION
The specific immunoadjuvant effects of AB4 have been demonstrated to modulate the growth and maturation of immune organs and enhance the secretion and cellular activity of pertinent immune molecules. The utilization of network pharmacology, combined within and in vivo vitro assays, clarified the adjuvant function of AB4, which potentially involves the regulation of the TLR4/NF-κB signaling pathway.
Topics: Animals; Mice; Humans; NF-kappa B; Toll-Like Receptor 4; Network Pharmacology; Adjuvants, Immunologic; Cytokines; Saponins; Adjuvants, Pharmaceutic; Dendritic Cells
PubMed: 38176273
DOI: 10.1016/j.phymed.2023.155302 -
Microbial Biotechnology Jul 2023Antimicrobial resistance is a major obstacle for the treatment of infectious diseases and currently represents one of the most significant threats to global health.... (Review)
Review
Antimicrobial resistance is a major obstacle for the treatment of infectious diseases and currently represents one of the most significant threats to global health. Staphylococcus aureus remains a formidable human pathogen with high mortality rates associated with severe systemic infections. S. aureus has become notorious as a multidrug resistant bacterium, which when combined with its extensive arsenal of virulence factors that exacerbate disease, culminates in an incredibly challenging pathogen to treat clinically. Compounding this major health issue is the lack of antibiotic discovery and development, with only two new classes of antibiotics approved for clinical use in the last 20 years. Combined efforts from the scientific community have reacted to the threat of dwindling treatment options to combat S. aureus disease in several innovative and exciting developments. This review describes current and future antimicrobial strategies aimed at treating staphylococcal colonization and/or disease, examining therapies that show significant promise at the preclinical development stage to approaches that are currently being investigated in clinical trials.
Topics: Drug Resistance, Multiple, Bacterial; Staphylococcus aureus; Antimicrobial Cationic Peptides; Biological Products; Anti-Bacterial Agents; Adjuvants, Pharmaceutic; Drug Synergism; Immunoconjugates; Phage Therapy; Drug Development; Staphylococcal Infections; Humans
PubMed: 37178319
DOI: 10.1111/1751-7915.14268 -
Frontiers in Immunology 2019Extracellular adenosine is a potent endogenous immunosuppressive mediator critical to the maintenance of homeostasis in various normal tissues including the lung.... (Review)
Review
Extracellular adenosine is a potent endogenous immunosuppressive mediator critical to the maintenance of homeostasis in various normal tissues including the lung. Adenosine is either released from stressed or injured cells or generated from extracellular adenine nucleotides by the concerted action of the ectoenzymes ectoapyrase (CD39) and 5' ectonucleotidase (CD73) that catabolize ATP to adenosine. An acute CD73-dependent increase of adenosine in normal tissues mostly exerts tissue protective functions whereas chronically increased adenosine-levels in tissues exposed to DNA damaging chemotherapy or radiotherapy promote pathologic remodeling processes and fibrosis for example in the skin and the lung. Importantly, cancer cells also express CD73 and high CD73 expression in the tumor tissue has been linked to poor overall survival and recurrence free survival in patients suffering from breast and ovarian cancer. CD73 and adenosine support growth-promoting neovascularization, metastasis, and survival in cancer cells. In addition, adenosine can promote tumor intrinsic or therapy-induced immune escape by various mechanisms that dampen the immune system. Consequently, modulating CD73 or cancer-derived adenosine in the tumor microenvironment emerges as an attractive novel therapeutic strategy to limit tumor progression, improve antitumor immune responses, avoid therapy-induced immune deviation, and potentially limit normal tissue toxicity. However, the role of CD73/adenosine signaling in the tumor and normal tissue responses to radiotherapy and its use as therapeutic target to improve the outcome of radiotherapy approaches is less understood. The present review will highlight the dual role of CD73 and adenosine in tumor and tissue responses to radiotherapy with a special focus to the lung. It will also discuss the potential benefits and risks of pharmacologic modulation of the CD73/adenosine system to increase the therapeutic gain of radiotherapy or combined radioimmunotherapy in cancer treatment.
Topics: 5'-Nucleotidase; Adenosine; Adjuvants, Pharmaceutic; Animals; Humans; Immunomodulation; Molecular Targeted Therapy; Radiotherapy; Receptors, Purinergic P1; Signal Transduction
PubMed: 31024543
DOI: 10.3389/fimmu.2019.00698 -
International Journal of Molecular... Aug 2023In recent years, several types of platelet concentrates have been investigated and applied in many fields, particularly in the musculoskeletal system. Platelet-rich... (Review)
Review
In recent years, several types of platelet concentrates have been investigated and applied in many fields, particularly in the musculoskeletal system. Platelet-rich fibrin (PRF) is an autologous biomaterial, a second-generation platelet concentrate containing platelets and growth factors in the form of fibrin membranes prepared from the blood of patients without additives. During tissue regeneration, platelet concentrates contain a higher percentage of leukocytes and a flexible fibrin net as a scaffold to improve cell migration in angiogenic, osteogenic, and antibacterial capacities during tissue regeneration. PRF enables the release of molecules over a longer period, which promotes tissue healing and regeneration. The potential of PRF to simulate the physiology and immunology of wound healing is also due to the high concentrations of released growth factors and anti-inflammatory cytokines that stimulate vessel formation, cell proliferation, and differentiation. These products have been used safely in clinical applications because of their autologous origin and minimally invasive nature. We focused on a narrative review of PRF therapy and its effects on musculoskeletal, oral, and maxillofacial surgeries and dermatology. We explored the components leading to the biological activity and the published preclinical and clinical research that supports its application in musculoskeletal therapy. The research generally supports the use of PRF as an adjuvant for various chronic muscle, cartilage, and tendon injuries. Further clinical trials are needed to prove the benefits of utilizing the potential of PRF.
Topics: Humans; Blood Platelets; Cartilage; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Fibrin
PubMed: 37628786
DOI: 10.3390/ijms241612608 -
International Journal of Molecular... May 2023In recent decades, vaccines have been extraordinary resources to prevent pathogen diffusion and cancer. Even if they can be formed by a single antigen, the addition of... (Review)
Review
In recent decades, vaccines have been extraordinary resources to prevent pathogen diffusion and cancer. Even if they can be formed by a single antigen, the addition of one or more adjuvants represents the key to enhance the response of the immune signal to the antigen, thus accelerating and increasing the duration and the potency of the protective effect. Their use is of particular importance for vulnerable populations, such as the elderly or immunocompromised people. Despite their importance, only in the last forty years has the search for novel adjuvants increased, with the discovery of novel classes of immune potentiators and immunomodulators. Due to the complexity of the cascades involved in immune signal activation, their mechanism of action remains poorly understood, even if significant discovery has been recently made thanks to recombinant technology and metabolomics. This review focuses on the classes of adjuvants under research, recent mechanism of action studies, as well as nanodelivery systems and novel classes of adjuvants that can be chemically manipulated to create novel small molecule adjuvants.
Topics: Humans; Aged; Adjuvants, Immunologic; Vaccines; Immunologic Factors; Adjuvants, Pharmaceutic; Antiviral Agents
PubMed: 37298177
DOI: 10.3390/ijms24119225