Immunoregulation
Volume:6 Issue: 2, Winter 2023

The long COVID-19 syndrome is a complex clinical state that lasts for several months and extends beyond the initial acute infectious phase. More than 200 known symptoms impact two or more organ systems. The most common symptoms include arthralgia, weakness, exhaustion, low effort tolerance, cognitive impairment, poor focus, palpitations, and chest pain. Approximately 65 million people globally are affected by long coronavirus disease (COVID-19), calculated from a conservative estimate of 10% of infected individuals and over 651 million officially recorded COVID-19 cases globally. The actual number is likely much greater because of numerous unregistered cases. The estimated incidence is 10% to 30% for non-hospitalized cases, 50% to 70% for hospitalized cases, and 10% to 12% for vaccinated cases.

Cell therapy, especially with mesenchymal stem cells (MSCs), is a potent treatment for many diseases or disorders. Meanwhile, MSCs-based cell-free products, such as extracellular vesicles (EVs) have been suggested as an alternative to MSCs. These MSC-EVs have been used in different trials to treat various inflammatory-dependent disorders. MSCs, according to their isolated tissue source, could present different therapeutic features and their derived EVs. One of the new sources for MSC isolation is amniotic fluid (AF). In addition, other than MSCs, new studies have used AF as an acceptable source for EV isolation. These isolated EVs from AF (AF-EVs) or AF-derived MSCs EVs (AF-MSC-EVs) have been used in different in-vitro and animal studies to treat a wide variety of inflammatory-dependent pathological conditions due to their confirmed anti-inflammatory potentials (through suppressing different pro-inflammatory cytokines). Meanwhile, in other conditions requiring repairing properties (e.g. wound healing or myocardial infarction), considering their regenerative and angiogenic potentials, these EVs have shown proper therapeutic results. Furthermore, other than the in-vitro and animal studies, AF-EVs containing treatment have successfully been used in some clinical trials and showed no adverse events among the patients and expressed potent anti-inflammatory properties through suppression of two very important pro-inflammatory cytokines, namely interleukin 6 and tumor necrosis factor α. Accordingly, AF-EVs and AF-MSC-EVs could be suitable choices for treatment due to their anti-inflammatory and regenerative properties. However, further clinical studies are needed.

The respiratory system is continually exposed to various harmful agents, which is why DNA repair is required. This comprises injury, inflammation, and other contents that are toxic and can cause damage to its genes. To eliminate the impact of DNA damage and restore cellular function, three pathways of repair are induced as follows: base excision repair, nucleotide excision repair (NER), and double-strand break pathway. However, such healing responses can be downregulated by long-term or severe injuries resulting in decreased recovery ability and predisposition to various diseases, such as lung cancer, chronic obstructive pulmonary disease (COPD), and fibrosis of the lungs. The generation of reactive oxygen species (ROS) during inflammation alters DNA and damages tissues. Despite this, inflammation will affect the initiation of tissue repair as well as DNA damage through the creation of ROS in this intricate process that occurs partly through innate immune responses and cytokine signaling. Cytotoxic processes hamper these fixing pathways of damaged genetic materials by inhibiting enzymes involved in DNA reparations and genes linked to repairs, thereby enhancing the risks of mutagenesis, carcinogenesis, and progressive diseases. Hence, the relationship between DNA repair and inflammatory reactions is crucial for lung health. It plays a major role in the pathophysiology of illnesses, such as cancer, COPD, fibrosis, and asthma. Inflammation and DNA damage are positively associated because they form a positive feedback loop that promotes disease and tissue pathology progression. DNA injury activates inflammation because immune cells are attracted to the site of injury, which in turn produces more oxidant molecules damaging the DNA. The evaluation of this relationship may help find approaches for reducing DNA damage, protecting genomic integrity, and preventing the progression of respiratory diseases.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammatory processes that result in joint swelling, inflammation, and the onset of pain. This discomfort and pathological condition exhibit a gradual rise in scale and become more intense. Even though pharmacotherapy like disease-modifying antirheumatic drugs (DMARDs) and biologics has improved, there is still a need for more focused treatments that cause less harm. This study examines how treatments for RA have changed over time, focusing on the shift from traditional medicines to new, creative ways to combine medicine with immune-engineering therapies. DMARDs are still the most common way to treat RA. On the other hand, biologics and Janus kinase inhibitors are options for people who do not react to their first medications. The development of nanomedicines and hydrogels is an exciting new area of study because they make it possible for more precise spread and less overall toxicity of the medicine. The early research suggests that these innovative approaches could greatly improve the effectiveness of therapy by delivering drugs directly to the site of inflammation while also reducing the severity of any side effects that might occur. RA care is quickly expanding beyond the traditional use of drugs to include more modern ways of managing medications and also personalized healing methods.

Gonadotropin hormone-releasing hormone (GnRH) is a peptide involved in mammals’ fertility and may also serve as a candidate target for cancer immunotherapy. Immunonsterilization is known as a proper alternative to surgical castration and has been advocated by European countries in recent years. Immunization with GnRH can effectively inhibit the secretion of gonadotropins and cause infertility in both genders of mammals. In this study, a recombinant trimer of GnRH is designed and expressed in a prokaryotic system.  A construct containing GnRH trimer was designed and prepared using gene synthesis. A cloning site was embedded and connected to the GnRH using a linker to further clone any protein of interest. The construct was subcloned into a pET-32a+ plasmid vector. The recombinant vector was transferred to BL21, an Escherichia coli strain, and the expression was induced using isopropyl β- d-1-thiogalactopyranoside (IPTG). The cell lysate was prepared using lysis buffer and nickel affinity chromatography purification. The GnRH expression was evaluated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis after protein purification. The cloning was verified using a polymerase chain reaction (PCR) followed by sequencing the recombinant vector. The result of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis verified the recombinant protein’s expression and the purification process’s function. The GnRH was properly cloned and expressed in BL21. The results also verified the reliability of the purification process. The construct design allows the researchers to express another peptide sequence attached to the GnRH using the embedded linker to improve the stability and antigenicity. A stable recombinant GnRH would be applied in immunocastration and cancer immunotherapies.

Melatonin, an endogenously produced indoleamine, is a highly effective antioxidant and free radical scavenger. This study investigates the potential antioxidant effects of melatonin in birds exposed to conditions promoting pulmonary hypertension syndrome (PHS) under cold stress.  Two groups of birds were offered different concentrations of melatonin (0.2% and 0.4%), while a control group received no melatonin treatment. Serum and cardiac tissue samples were collected to evaluate glutathione peroxidase (GPX) and superoxide dismutase 1 (SOD1) activities and the relative expression of GPX and SOD1 genes.  The results showed a significant decrease in the right ventricular to total ventricular weight ratio in the melatonin 0.4% supplemented group compared to the control. Melatonin supplementation at 0.2% and 0.4% levels led to lower levels of malondialdehyde (MDA) in the serum and heart compared to the control group, indicating reduced lipid peroxidation. Both melatonin groups exhibited increased serum/cardiac (GPX) activities compared to the control group; however, the serum SOD1 activity was only increased in the melatonin 0.4% group of birds compared to the control group. Furthermore, the melatonin-0.2% and -0.4% groups displayed decreased relative gene expression of GPX and SOD1 compared to the control group.  Melatonin, especially with a dose of 0.4%, when used as an antioxidant agent, can be beneficial in reducing the severity of PHS and heart right ventricular failure in birds.

The Razi-Cov-Pars vaccine, a recombinant protein vaccine developed in Iran, has undergone evaluation in three dosage strengths across three clinical trial phases. In phase I, volunteers received one of three dosages (5, 10, and 20 μg) corresponding to low, medium, and high strengths. 

This study assessed the long-term in vitro immune status of the Razi-Cov-Pars vaccine by transferring lymphocyte supernatants (SN) from individuals vaccinated for 8 months to lymphocytes from individuals vaccinated for 16 months and non-vaccinated healthy individuals. Immunological parameters were evaluated using the 3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide assay for stimulation index and reverse transcription polymerase chain reaction for interleukin 10, transforming growth factor-ß (TGF-ß) and TGF-α levels.

The findings revealed that lymphocyte SN from individuals vaccinated for 8 months significantly enhanced the proliferation of lymphocytes from individuals vaccinated for 16 months with the licensed 10 μg strength vaccine. This suggests that the Razi-Cov-Pars vaccine may have long-term effects on lymphocyte proliferation and immune response. Notably, there was a significant increase in TGF-α levels across all vaccine strengths, hinting at the potential role of TGF-α in long-term immune processes following vaccination with Razi-Cov-Pars. Additionally, there was a marked increase in interleukin-10 levels in all vaccinated groups, indicating active pro-inflammatory elements in the SN. TGF-β expression significantly increased in the high-strength vaccine group, whereas no notable difference was observed in the low and medium-strength groups.

We detected a significant stimulation in the lymphocytes isolated from vaccinated individuals after 16 months by measurement of proliferative potential and cytokine gene expression thereby assessing the long-term effect of the vaccine.

One of the main reasons for tooth loss and functional incompatibility of dentition is periodontitis which is a multi-factorial disease. Among the main reasons for periodontitis is inflammation.

Hypothesis:

 Some keystone bacteria, such as Prophyromonas gingivalis with a notable number of virulence factors could activate and modify inflammatory pathways in gingiva. A well-established therapy for this disease is topical antibiotics; however, these treatments have side effects and could promote antibiotic-resistant infections as well. Such antibiotic-resistant infections are a group of periodontitis with a severely complicated treatment approach that could fail. Thus, new strategies need to be developed for treatment-resistant (antibiotic-resistant) periodontitis. In the past decades, many randomized controlled clinical trials have shown that mesenchymal stromal cells (MSCs) could treat inflammatory-dependent diseases or disorders. In addition to MSCs, the anti-inflammatory effects of their extracellular vesicles (EVs) have also been studied in the clinic. 

Considering the anti-inflammatory potential of MSCs-derived EVs, it could be hypothesized that local delivery of these EVs could be an effective method for periodontal treatment due to the accessible location of the periodontium.

This study suggests further in vivo studies and randomized clinical trials on the potential effects of MSCs-derived EVs on periodontal disease treatment.