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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 -
Frontiers in Immunology 2023Mucosal vaccines have great potential and advantages in preventing infection caused by multiple pathogens. In developing mucosal vaccines, the biggest challenge comes... (Review)
Review
Mucosal vaccines have great potential and advantages in preventing infection caused by multiple pathogens. In developing mucosal vaccines, the biggest challenge comes from finding safe and effective adjuvants and drug delivery systems. Great progress has been made in the generation of mucosal adjuvants using detoxified bacterial toxin derivatives, pathogen-related molecules, cytokines, and various vaccine delivery systems. However, many problems, relating to the safety and efficacy of mucosal vaccine adjuvants, remain. Certain natural substances can boost the immune response and thus could be used as adjuvants in vaccination. These natural-product-based immune adjuvants have certain advantages over conventional adjuvants, such as low toxicity, high stability, and low cost of production. In this review, we summarize the latest natural-product-based immune adjuvants, and discuss their properties and clinical applications.
Topics: Adjuvants, Vaccine; Biological Products; Vaccines; Vaccination; Adjuvants, Immunologic; Adjuvants, Pharmaceutic
PubMed: 37090704
DOI: 10.3389/fimmu.2023.1152855 -
Cells Dec 2022The vertebrate immune system functions to eliminate invading foreign nucleic acids and foreign proteins from infectious diseases and malignant tumors. Because pathogens... (Review)
Review
The vertebrate immune system functions to eliminate invading foreign nucleic acids and foreign proteins from infectious diseases and malignant tumors. Because pathogens and cancer cells have unique amino acid sequences and motifs (e.g., microbe-associated molecular patterns, MAMPs) that are recognized as "non-self" to the host, immune enhancement is one strategy to eliminate invading cells. MAMPs contain nucleic acids specific or characteristic of the microbe and are potential candidates for immunostimulants or adjuvants. Adjuvants are included in many vaccines and are a way to boost immunity by deliberately administering them along with antigens. Although adjuvants are an important component of vaccines, it is difficult to evaluate their efficacy ex vivo and in vivo on their own (without antigens). In addition, inflammation induced by currently candidate adjuvants may cause adverse events, which is a hurdle to their approval as drugs. In addition, the lack of guidelines for evaluating the safety and efficacy of adjuvants in drug discovery research also makes regulatory approval difficult. Viral double-stranded (ds) RNA mimics have been reported as potent adjuvants, but the safety barrier remains unresolved. Here we present ARNAX, a noninflammatory nucleic acid adjuvant that selectively targets Toll-like receptor 3 (TLR3) in antigen-presenting dendritic cells (APCs) to safely induce antigen cross-presentation and subsequently induce an acquired immune response independent of inflammation. This review discusses the challenges faced in the clinical development of novel adjuvants.
Topics: Humans; Adjuvants, Immunologic; Vaccines; Immune System; Adjuvants, Pharmaceutic; Antigens; Inflammation; Nucleic Acids
PubMed: 36552770
DOI: 10.3390/cells11244006 -
Pharmacology & Therapeutics Dec 2018Inflammatory pain is the most common type of pain that is treated clinically. The use of currently available treatments (classic analgesics - NSAIDs, paracetamol and... (Review)
Review
Inflammatory pain is the most common type of pain that is treated clinically. The use of currently available treatments (classic analgesics - NSAIDs, paracetamol and opioids) is limited by insufficient efficacy and/or side effects/tolerance development. Antiepileptic drugs (AEDs) are widely used in neuropathic pain treatment, but there is substantial preclinical evidence on their efficacy against inflammatory pain, too. In this review we focus on gabapentinoids (gabapentin and pregabalin) and dibenzazepine AEDs (carbamazepine, oxcarbazepine, and recently introduced eslicarbazepine acetate) and their potential for relieving inflammatory pain. In models of somatic, visceral and trigeminal inflammatory pain, that have a translational value for inflammatory conditions in locomotor system, viscera and head/face, AEDs have demonstrated analgesic activity. This activity was mostly consistent, dependent on the dose and largely independent on the site of inflammation and method of its induction, nociceptive stimuli, species, specific drug used, its route of administration and dosing schedule. AEDs exerted comparable efficacy with classic analgesics. Effective doses of AEDs are lower than toxic doses in animals and, when expressed as equivalent human doses, they are largely overlapping with AEDs doses already used in humans for treating epilepsy/neuropathic pain. The main mechanism of antinociceptive/antihyperalgesic action of gabapentinoids in inflammatory pain models seems to be αδ-dependent suppression of voltage-gated calcium channels in primary sensory neurons that leads to reduced release of neurotransmitters in the spinal/medullar dorsal horn. The suppression of NMDA receptors via co-agonist binding site primarily at spinal sites, activation of various types of K channels at spinal and peripheral sites, and activation of noradrenergic and serotonergic descending pain modulatory pathways may also contribute. Inhibition of voltage-gated sodium channels along the pain pathway is probably the main mechanism of antinociceptive/antihyperalgesic effects of dibenzazepines. The recruitment of peripheral adrenergic and purinergic mechanisms and central GABAergic mechanisms may also contribute. When co-administered with classic/other alternative analgesics, AEDs exerted synergistic/additive interactions. Reviewed data could serve as a basis for clinical studies on the efficacy/safety of AEDs as analgesics/adjuvants in patients with inflammatory pain, and contribute to the improvement of the treatment of various inflammatory pain states.
Topics: Adjuvants, Pharmaceutic; Analgesics; Animals; Anticonvulsants; Dibenzazepines; Drug Evaluation, Preclinical; Gabapentin; Humans; Inflammation; Pain; Pregabalin
PubMed: 29909236
DOI: 10.1016/j.pharmthera.2018.06.002 -
Frontiers in Immunology 2023Rhizoma Bolbostemmatis, the dry tuber of , has being used for the treatment of acute mastitis and tumors in traditional Chinese medicine. In this study, tubeimoside...
Rhizoma Bolbostemmatis, the dry tuber of , has being used for the treatment of acute mastitis and tumors in traditional Chinese medicine. In this study, tubeimoside (TBM) I, II, and III from this drug were investigated for the adjuvant activities, structure-activity relationships (SAR), and mechanisms of action. Three TBMs significantly boosted the antigen-specific humoral and cellular immune responses and elicited both Th1/Th2 and Tc1/Tc2 responses towards ovalbumin (OVA) in mice. TBM I also remarkably facilitated mRNA and protein expression of various chemokines and cytokines in the local muscle tissues. Flow cytometry revealed that TBM I promoted the recruitment and antigen uptake of immune cells in the injected muscles, and augmented the migration and antigen transport of immune cells to the draining lymph nodes. Gene expression microarray analysis manifested that TBM I modulated immune, chemotaxis, and inflammation-related genes. The integrated analysis of network pharmacology, transcriptomics, and molecular docking predicted that TBM I exerted adjuvant activity by interaction with SYK and LYN. Further investigation verified that SYK-STAT3 signaling axis was involved in the TBM I-induced inflammatory response in the C2C12 cells. Our results for the first time demonstrated that TBMs might be promising vaccine adjuvant candidates and exert the adjuvant activity through mediating the local immune microenvironment. SAR information contributes to developing the semisynthetic saponin derivatives with adjuvant activities.
Topics: Female; Mice; Animals; Molecular Docking Simulation; Adjuvants, Immunologic; Saponins; Cytokines; Adjuvants, Pharmaceutic
PubMed: 36845089
DOI: 10.3389/fimmu.2023.1108244 -
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 -
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 -
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 -
Medication-related osteonecrosis of the jaw: evolving research for multimodality medical management.Supportive Care in Cancer : Official... Mar 2024Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating side effect of antiresorptive and antiangiogenic agents that can lead to progressive bone... (Review)
Review
PURPOSE
Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating side effect of antiresorptive and antiangiogenic agents that can lead to progressive bone destruction in the maxillofacial region. Dental surgery, including tooth extractions, commonly trigger the onset of MRONJ. While guidelines suggest avoiding extraction when possible, complete avoidance is not always feasible, as necrosis can develop from dental and periodontal disease without dental procedures. The goal of this article is to provide an update review of current preventive and therapeutic approaches for MRONJ.
METHODS
A comprehensive electronic search was conducted on PubMed/MEDLINE, Embase, and Scopus databases. All English articles encompassing randomized controlled trials, systematic reviews, observational studies, and case studies were reviewed. The current medical treatments and adjuvant therapies for managing MRONJ patients were critically assessed and summarized.
RESULTS
Pentoxifylline and alpha tocopherol (PENT-E), teriparatide, photobiomodulation (PBM), photodynamic therapy (PDT), and the use of growth factors have shown to enhance healing in MRONJ patients. Implementing these methods alone or in conjunction with surgical treatment has been linked to reduced discomfort and improved wound healing and increased new bone formation.
DISCUSSION
While several adjuvant treatment modalities exhibit promising results in facilitating the healing process, current clinical practice guidelines predominantly recommend antibiotic therapy as a non-surgical approach, primarily addressing secondary infections in necrotic areas. However, this mainly addresses the potential infectious complication of MRONJ. Medical approaches including PENT-E, teriparatide, PBM, and PDT can result in successful management and should be considered prior to taking a surgical approach. Combined medical management for both preventing and managing MRONJ holds potential for achieving optimal clinical outcomes and avoiding surgical intervention, requiring further validation through larger studies and controlled trials.
Topics: Humans; Adjuvants, Immunologic; Adjuvants, Pharmaceutic; Combined Modality Therapy; Osteonecrosis; Teriparatide; Jaw Diseases
PubMed: 38443685
DOI: 10.1007/s00520-024-08388-4