Atherosclerosis is one type of cardiovascular disease (CVD) in which activation of the NLRP3 inflammasome and toll-like receptor (TLR) pathways is implicated. One of the most effective treatments for ...atherosclerosis is the use of statin medications. Recent studies have indicated that statins, in addition to their lipid-lowering effects, exert inhibitory and/or stimulatory effects on the NLRP3 inflammasome and TLRs. Some of the statins lead to activation of the inflammasome and subsequently cause secretion of IL-1β and IL-18. Thus, these actions may further aggravate the disease. On the other hand, some statins cause inhibition of the inflammasome or TLRs and along with lipid-lowering, help to improve the disease by reducing inflammation. In this article, we discuss these contradictory studies and the mechanisms of action of statins on the NLRP3 inflammasome and TLR pathways. The dose-dependent effects of statins on the NLRP3 complex are related to their chemistry, pharmacokinetic properties, and danger signals. Lipophilic statins have more pleiotropic effects on the NLRP3 complex in comparison to hydrophilic statins. Statins can suppress TLR4/MyD88/NF-ĸB signaling and cause an immune response shift to an anti-inflammatory response. Furthermore, statins inhibit the NF-ĸB pathway by decreasing the expression of TLRs 2 and 4. Statins are cost-effective drugs, which should have a continued future in the treatment of atherosclerosis due to both their immune-modulating and lipid-lowering effects.
Gold nanoparticles (GNPs) have been recently applied for various diagnostic and therapeutic purposes. The unique properties of these nanoparticles (NPs), such as relative ease of synthesis in various ...sizes, shapes and charges, stability, high drug-loading capacity and relative availability for modification accompanied by non-cytotoxicity and biocompatibility, make them an ideal field of research in bio-nanotechnology. Moreover, their potential to alleviate various inflammatory factors, nitrite species, and reactive oxygen production and the capacity to deliver therapeutic agents has attracted attention for further studies in inflammatory and autoimmune disorders. Furthermore, the characteristics of GNPs and surface modification can modulate their toxicity, biodistribution, biocompatibility, and effects. This review discusses in vitro and in vivo effects of GNPs and their functionalized forms in managing various autoimmune disorders (Ads) such as rheumatoid arthritis, type 1 diabetes, and multiple sclerosis.
Granulation tissue is a primary source of otorrhea in the ear, particularly after surgery, and may develop complications in patients. Hence, discovering an efficient treatment is crucial for this ...disorder.
This study aimed to evaluate the mitomycin drops efficacy for germination prevention during the recovery process after mastoidectomy. Our purpose was to introduce novel treatment options in some conditions in which we could not reconstitute the cavity to prevent the possible germination.
This clinical trial was performed on 52 patients undergoing mastoidectomy. Patients were randomly divided into two groups (26 patients in the mitomycin group and 26 patients in the placebo group). After drug administration, the granulation tissue and complications were recorded. All statistical analysis was performed using SPSS version 21.
The results of our study showed that mitomycin administration in patients undergoing mastoidectomy significantly reduced the formation of the granulation tissue in the first and third months after surgery (P < 0.05), which is associated with increased patient satisfaction (P < 0.05).
The germ formation after mastoidectomy is so common. Since mitomycin administration decreased the incidence of germ formation, it can be proposed as a suggestive treatment in all patients to increase surgical quality and decrease complications include granulation formation.
•SLIT is an efficient and non-invasive route for treatment of allergic disorders.•Adjuvants and delivery systems could enhance the efficacy of SLIT.
Allergen-specific sublingual immunotherapy (SLIT), ...a safe and efficient route for treating type I hypersensitivity disorders, requires high doses of allergens. SLIT is generally performed without adjuvants and delivery systems. Therefore, allergen formulation with appropriate presentation platforms results in improved allergen availability, targeting the immune cells, inducing regulatory immune responses, and enhancing immunotherapy's efficacy while decreasing the dose of the allergen. In this review, we discuss the adjuvants and delivery systems that have been applied as allergen-presentation platforms for SLIT. These adjuvants include TLRs ligands, 1α, 25-dihydroxy vitamin D3, galectin-9, probiotic and bacterial components that provoke allergen-specific helper type-1 T lymphocytes (TH1), and regulatory T cells (Tregs). Another approach is encapsulation or adsorption of the allergens into a particulate vector system to facilitate allergen capture by tolerogenic dendritic cells. Also, we proposed strategies to increasing the efficacy of SLIT via new immunopotentiators and carrier systems in the future.
Allergen-specific Immunotherapy (AIT) is the main therapeutic strategy to control and treat allergic disorders. Intranasal Immunotherapy (INIT) was introduced as a needle-free, noninvasive, and ...efficient approach among various routes of allergen administration. Since direct exposure of nasal mucosa to allergen extracts could induce local and systemic reactions, recent studies focus on establishing novel formulations using various delivery systems and adjuvants to improve INIT efficacy. This review categorizes and describes natural and synthetic micro/nanoparticles such as chitosan, PLGA, liposome, exosome, and nano-emulation droplets used as delivery systems or immunomodulatory and immune-regulatory agents. Also, multiple microbial agents, including probiotics, mycobacterial and viral components, TLR ligands, and biologic agents, i.e., antibody fragments, recombinant cytokines, vitamin A, and pulsed dendritic cells (DCs), are other platforms that are discussed. In addition, future perspectives and proposed strategies to help INIT were provided.
Mesenchymal stem cells (MSCs) are a population of non-hematopoietic and self-renewing cells characterized by the potential to differentiate into different cell subtypes. MSCs have interesting ...features which have attracted a lot of attention in various clinical investigations. Some basic features of MSCs are including the weak immunogenicity (absence of MHC-II and costimulatory ligands accompanied by the low expression of MHC-I) and the potential of plasticity and multi-organ homing via expressing related surface molecules. MSCs by immunomodulatory effects could also ameliorate several immune-pathological conditions like graft-versus-host diseases (GVHD). The efficacy and potency of MSCs are the main objections of MSCs therapeutic applications. It suggested that improving the MSC immunosuppressive characteristic via genetic engineering to produce therapeutic molecules consider as one of the best options for this purpose. In this review, we explain the functions, immunologic properties, and clinical applications of MSCs to discuss the beneficial application of genetically modified MSCs in GVHD.
Abstract Nanoparticles (NPs) that target multiple transport mechanisms facilitate targeted delivery of active therapeutic agents to the central nervous system (CNS) and improve therapeutic transport ...and efficacy across the blood‐brain barrier (BBB). CNS nanotherapeutics mostly target neurons and endothelial cells, however, microglial immune cells are the first line of defense against neuronal damage and brain infections. Through triggering release of inflammatory cytokines, chemokines and proteases, microglia can however precipitate neurological damage—a significant factor in neurodegenerative diseases. Thus, microglial inhibitory agents are attracting much attention among those researching and developing novel treatments for neurodegenerative disorders. The most established inhibitors of microglia investigated to date are resveratrol, curcumin, quercetin, and minocycline. Thus, there is great interest in developing novel agents that can bypass or easily cross the BBB. One such approach is the use of modified‐nanocarriers as, or for, delivery of, therapeutic agents to the brain and wider CNS. For microglial inhibition, polymeric NPs are the preferred vehicles for choice. Here, we summarize the immunologic and neuroinflammatory role of microglia, established microglia inhibitor agents, challenges of CNS drug delivery, and the nanotherapeutics explored for microglia inhibition to date. We also discuss applications of the currently considered “most useful” polymeric NPs for microglial‐inhibitor drug delivery in CNS‐related diseases.
Background
Acute renal dysfunction still constitutes a highly significant obstacle to renal transplantation outcome. Kidney injury molecule-1 is highly upregulated in proximal tubular cells and shed ...into the urine and blood circulation following kidney injury. The aim of current cohort study was to evaluate the urine KIM-1 (uKIM-1) mRNA expression level and its protein concentration in blood and urine samples to determine whether sequential monitoring of KIM-1 in renal allograft recipients is a reliable biomarker for predicting the clinical status and outcome.
Methods
Both uKIM-1 mRNA expression level and the level of serum and uKIM-1 protein concentration in the 52 renal transplant recipients were respectively quantified using real-time PCR and ELISA methods at 2, 90 and 180 days after transplantation.
Result
KIM-1 mRNA and protein expression level in the blood and urine samples of patients with graft dysfunction was significantly higher than patients with well-functioning graft on days 2, 90 and 180 after transplantation. Receiver-operating characteristic curve analysis of mRNA and protein expression levels showed that urinary and blood KIM-1 at months 3 and 6 could predict acute renal dysfunction at 6 months and 1 year after transplantation.
Conclusion
Sequential monitoring of uKIM-1 mRNA expression level and its protein concentration in the serum and urine samples of renal transplant patients suggests that KIM-1 could be a sensitive and specific biomarker for early diagnosis and prognosis of kidney allograft injury.
•SLIT is an efficient and non-invasive alternative for SCIT.•AuNPs are biocompatible carriers for diagnostic and therapeutic approaches.•DC-specific aptamers could be applied for targeted drug ...delivery.
Sublingual immunotherapy (SLIT) was introduced to deliver allergens in an effective and non-invasive route, which can be considered as an alternative for allergen-specific subcutaneous immunotherapy (SCIT). On the other hand, the use of gold nanoparticles (AuNPs) in allergen delivery has beneficial effects on sublingual immunotherapy. In addition, the molecular targeting agents like aptamers (Apt), have been widely applied for targeted drug delivery. Therefore, the current study aimed to evaluate the effects of dendritic cells (DCs)-specific Aptamer-modified AuNPs coated with ovalbumin (OVA) on the improvement of the SLIT outcome in the mouse model of allergy.
AuNPs with approximately 15 nm diameter were prepared by citrate reduction of HAuCl4. Afterward, Apt-modified AuNP complex was prepared and OVA was then loaded onto this complex. Following sensitization of Balb/c mice to OVA, SLIT was performed with Apt-AuNPs containing 5 µg OVA twice a week for a 2-month period. Allergen-specific IgE in serum, as well as cytokines secretion of spleen cells, were analyzed using ELISA. Also, nasopharyngeal lavage Fluid (NALF) was collected for total and eosinophil counts. Moreover, the lungs were removed for histopathological examination.
SLIT with Apt-modified AuNPs complex containing 5 μg OVA, decreased the IgE levels compared to the other groups. Also, IL-4 production has significantly decreased in spleen cells, while TGF-β and IFN-γ have significantly increased. The assessment of NALF in the group treated by this complex showed a decrease in total cell as well as in eosinophil count. Also, the examination of lung tissues revealed that, in the group treated by this complex, inflammation and perivascular infiltration were lesser than the other groups, which were observed in only one vessel of tissue.
It was shown that, Sublingual immunotherapy with DC specific Apt-modified AuNPs containing 5 μg OVA can improve the Th1 and Treg immunomodulatory responses.
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