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Journal of the Formosan Medical... Oct 2023Oral cancer is a prevalent global issue, with oral squamous cell carcinoma constituting the majority of cases. Standard treatments like surgery, radiotherapy, and... (Review)
Review
Oral cancer is a prevalent global issue, with oral squamous cell carcinoma constituting the majority of cases. Standard treatments like surgery, radiotherapy, and chemotherapy are available but may have adverse effects. Molecular gene therapy, focusing on genetic mutations linked to oral cancer, presents a promising alternative.In this study, we evaluated 27 chemotherapeutic drugs and 63 Chinese herbal medicines for their effectiveness, categorized them by their cellular mechanisms, and identified potential adjuvant therapy candidates for oral cancer. Our findings highlight the impact of natural flavonoids on oral cancer cells, inducing apoptosis, and confirming their potential in molecular genetic analysis. In conclusion, the natural compounds present in Chinese herbal medicine, particularly flavonoids, offer a promising avenue to target specific genetic mutations in oral cancer cells. This approach may reduce the risks associated with oral cancer treatment and pave the way for innovative adjuvant therapies.
PubMed: 37919197
DOI: 10.1016/j.jfma.2023.10.009 -
Vaccines Oct 2023Influenza vaccines faced significant challenges in achieving sufficient protective efficacy and production efficiency in the past. In recent decades, novel influenza... (Review)
Review
Influenza vaccines faced significant challenges in achieving sufficient protective efficacy and production efficiency in the past. In recent decades, novel influenza vaccines, characterized by efficient and scalable production, advanced platforms, and new adjuvant technologies, have overcome some of these weaknesses and have been widely licensed. Furthermore, researchers are actively pursuing the development of next-generation and universal influenza vaccines to provide comprehensive protection against potential pandemic subtypes or strains. However, new challenges have emerged as these novel vaccines undergo evaluation and authorization. In this review, we primarily outline the critical challenges and advancements in research and development (R&D) and highlight the improvements in regulatory responses for influenza vaccines.
PubMed: 37896976
DOI: 10.3390/vaccines11101573 -
BJU International Apr 2024To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the...
OBJECTIVE
To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients.
PATIENTS AND METHODS
In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models.
RESULTS
A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001).
CONCLUSION
In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.
PubMed: 38627025
DOI: 10.1111/bju.16371 -
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 -
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 -
International Journal of Biological... Dec 2023Actinidia eriantha polysaccharide (AEPS) is a potent adjuvant with dual Th1 and Th2 potentiating activity. linc-AAM has been previously proved to facilitate the...
Actinidia eriantha polysaccharide (AEPS) is a potent adjuvant with dual Th1 and Th2 potentiating activity. linc-AAM has been previously proved to facilitate the expression of immune response genes (IRGs) in AEPS-activated RAW264.7 macrophages. However, its role in mediating adjuvant activity of AEPS remains to be elucidated. In this study, bone marrow-derived macrophages (BMDMs) from wide-type (WT) and linc-AAM knockout C57BL/6J mice treated with AEPS were subjected to transcriptome sequencing and bioinformatic analysis. linc-AAM deficiency inhibited M1 and M2 immune responses in BMDMs induced by AEPS. In mechanisms, AEPS facilitated the expression of IRGs and activated BMDMs through NF-κB-linc-AAM-JAK/STAT axis. Furthermore, linc-AAM knockout inhibited cytokine and chemokine production, immune cell recruitment as well as immune cell migration to draining lymph nodes at peritoneal cavity in mice induced by AEPS. More importantly, linc-AAM deletion reduced the adjuvant activity of APES on antigen-specific cellular and humoral immune responses to ovalbumin in mice. This study has for the first time demonstrated the role of lncRNAs in regulating the adjuvant activity of polysaccharides and its mechanisms. These findings expanded current knowledge on the mechanism of action of adjuvant and provide a new target for the design and development of vaccine adjuvants.
Topics: Animals; Mice; Actinidia; Mice, Inbred C57BL; Adjuvants, Immunologic; Macrophages; Adjuvants, Pharmaceutic; Polysaccharides
PubMed: 37611690
DOI: 10.1016/j.ijbiomac.2023.126440 -
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 -
European Journal of Immunology Feb 2024Vaccination is considered one of the major milestones in modern medicine, facilitating the control and eradication of life-threatening infectious diseases. Vaccine... (Review)
Review
Vaccination is considered one of the major milestones in modern medicine, facilitating the control and eradication of life-threatening infectious diseases. Vaccine adjuvants are a key component of many vaccines, serving to steer antigen-specific immune responses and increase their magnitude. Despite major advances in the field of adjuvant research over recent decades, our understanding of their mechanism of action remains incomplete. This hinders our capacity to further improve these adjuvant technologies, so addressing how adjuvants induce and control the induction of innate and adaptive immunity is a priority. Investigating how adjuvant physicochemical properties, such as size and charge, exert immunomodulatory effects can provide valuable insights and serve as the foundation for the rational design of vaccine adjuvants. Most clinically applied adjuvants are particulate in nature and polymeric particulate adjuvants present advantages due to stability, biocompatibility profiles, and flexibility in terms of formulation. These properties can impact on antigen release kinetics and biodistribution, cellular uptake and targeting, and drainage to the lymphatics, consequently dictating the induction of innate, cellular, and humoral adaptive immunity. A current focus is to apply rational design principles to the development of adjuvants capable of eliciting robust cellular immune responses including CD8 cytotoxic T-cell and Th1-biased CD4 T-cell responses, which are required for vaccines against intracellular pathogens and cancer. This review highlights recent advances in our understanding of how particulate adjuvants, especially polymer-based particulates, modulate immune responses and how this can be used as a guide for improved adjuvant design.
Topics: Adjuvants, Vaccine; Tissue Distribution; Vaccines; Vaccination; Adaptive Immunity; Adjuvants, Immunologic; Antigens
PubMed: 37994660
DOI: 10.1002/eji.202350512 -
Life Sciences Dec 2023Traumatic brain injury and spinal cord injury are two distinct but fundamentally similar types of acute insults to the central nervous system (CNS) that often culminate... (Review)
Review
Traumatic brain injury and spinal cord injury are two distinct but fundamentally similar types of acute insults to the central nervous system (CNS) that often culminate in death or cognitive and motor impairment. Over the past decade, researchers have tapped into research to discover the potential role being played by gut bacteria in CNS. After an acute CNS injury, the altered composition of the gut microbiota disturbs the balance of the bidirectional gut-brain axis, aggravating secondary CNS injury, motor dysfunctions, and cognitive deficits, which worsens the patient's prognosis. Some of the well-known therapeutic interventions which can also be used as adjuvant therapy for alleviating CNS injuries include, the use of pro and prebiotics, fecal microbiota transplantation, and microbial engineering. In this review, we aim to discuss the importance of gut microbes in our nervous system, anatomy, and signaling pathways involved in regulating the gut-brain axis, the alteration of the gut microbiome in CNS injuries, and the therapeutic strategies to target gut microbiomes in traumatic CNS injuries.
Topics: Humans; Gastrointestinal Microbiome; Central Nervous System; Brain Injuries, Traumatic; Prebiotics; Spinal Cord Injuries; Brain
PubMed: 37865177
DOI: 10.1016/j.lfs.2023.122193 -
Drug Delivery and Translational Research Mar 2024Vaccines are the cornerstone of world health. The majority of vaccines are formulated as injectable products, facing the drawbacks of cold chain transportation,... (Review)
Review
Vaccines are the cornerstone of world health. The majority of vaccines are formulated as injectable products, facing the drawbacks of cold chain transportation, needle-stick injuries, and primary systemic immunity. Inhalable vaccines exhibited unique advantages due to their small dose, easy to use, quick effect, and simultaneous induction of mucosal and systemic responses. Facing global pandemics, especially the coronavirus disease 2019 (COVID-19), a majority of inhalable vaccines are in preclinical or clinical trials. A better understanding of advanced delivery technologies of inhalable vaccines may provide new scientific insights for developing inhalable vaccines. In this review article, detailed immune mechanisms involving mucosal, cellular, and humoral immunity were described. The preparation methods of inhalable vaccines were then introduced. Advanced nanotechnologies of inhalable vaccines containing inhalable nucleic acid vaccines, inhalable adenovirus vector vaccines, novel adjuvant-assisted inhalable vaccines, and biomaterials for inhalable vaccine delivery were emphatically discussed. Meanwhile, the latest clinical progress in inhalable vaccines for COVID-19 and tuberculosis was discussed.
Topics: Humans; Immunity, Mucosal; COVID-19 Vaccines; Vaccines; Nanotechnology; COVID-19
PubMed: 37747597
DOI: 10.1007/s13346-023-01431-7