ali mohammad mohseni majd

Sulfur mustard (SM), an alkylating chemical agent, targets several organs, particularly the respiratory system, and results in early and late toxic effects. Currently, there is a considerable lack of adequate medical countermeasures for SM-associated lung injury. Mesenchymal stem cells (MSCs) are characterized by their self-renewal properties and differentiation capacity into multiple cell lineages. These features provide MSCs with the unique ability to engraft into injured tissues and exert immunomodulatory and tissue-repairing effects. Recent congruent findings on the usefulness of MSCs in the context of SM-induced pulmonary injury have raised the promise of their therapeutic use; however, their potential protective mechanisms are still unknown. A better understanding of the therapeutic mechanism of MSCs involved in SM-pulmonary injury would help figure out new target options. Accordingly, this study discusses the opportunities and therapeutic mechanisms of MSCs in SM poisoning. Recent advances in the treatment of SM-induced lung injury and the therapeutic mechanisms of MSCs as possible new treatments are highlighted. The PubMed and Scopus databases for published studies on the therapeutic approach of SM-induced lung manifestations were searched with a focus on the therapeutic mechanisms of MSCs.

Sulfur mustard as a chemical warfare agent causes short and long-term pulmonary complications in its victims. MicroRNAs are known to act as remarkable regulators of biological pathways, monitoring, and treatment of diseases including respiratory problems. In this study, we investigated the expression of miR-106a-5p and miR-106b-5p, two regulators of TGF-β signaling, as well as their target molecule, TGFβ1I1, in peripheral blood mononuclear cells from SM-exposed individuals. A total of 70 veterans with SM-induced pulmonary complications were examined and compared to 35 gender and age-matched healthy controls. After clinical examination and pulmonary function tests, the severity of pulmonary complications was classified. Total RNA was extracted from PBMCs and the purity of extracted RNA samples was evaluated by a NanoDrop 2000. The miR-106a-5p, miR-106b-5p, and TGFβ1I1 expression levels were measured by real-time RT-PCR. The miR-106a-5p expression levels were significantly increased in both mild (P=0.015) and severe groups compared with the control group. The miR-106b-5p expression levels were considerably elevated in the severe group TGFβ1I1 expression levels were notably reduced in the severe group compared with the control group. Although, a slight decrease in TGFβ1I1 expression levels was observed in the mild group compared with the control. Our results indicate that exposure to sulfur mustard affects the expression of miR-106a-5p, miR-106b-5p, and their target gene, TGFβ1I1, in peripheral blood mononuclear cells. Considering the role of TGFβ1I1 in the regulation of TGF-β signaling, the mentioned changes might point to a potential mechanism by which SM exposure causes chronic pulmonary complications. In a ROC analysis, miR-106a-5p and miR-106b-5p potentially turned out to be a suitable diagnostic biomarker in the mild and severe categories of patients. Although, miR-106a-5p could be considered a better biomarker than miR-106b-5p.

The treatment of bladder cancer is usually performed by Bacillus Calmette-Guerin (BCG) instillation. BCG therapy is a common therapeutic method with fewer side effects compared with chemotherapy, radiotherapy, etc. BCG can also inhibit the progression and recurrence of bladder cancer by inducing apoptosis pathways, arrest cell cycle, autophagy, and neutrophil extracellular traps (NETs) formation. However, BCG therapy cannot be effective in the situation that the metastasis occurs. NETs are induced by BCG and help suppress the growth of tumor cells, especially in the primary stages of bladder cancer. Activated neutrophils can stimulate cellular pathways, such as autophagy and NETs release in the presence of microbial pathogenesis, inflammatory agents, and tumor cells. Autophagy can also regulate NETs formation and induce Reactive Oxygen Species (ROS) and NETs production. Moreover, miRNAs are key regulators of gene expression. These small non-coding RNAs are also considered as an essential factor in controlling tumor development. The interaction between BCG and miRNAs is still unclear. However, in the present study and for the first time, we intend to discuss the role of miRNAs in BCG therapy and how NETs formation can be effective on BCG performance to treat the bladder cancer.

Based on the reports, Aloe vera extract, a herbal medicine, has antimicrobial and anti-inflammatory effects. Also, this medicinal plant has considerable effects on innate immunity through cytokine secretion which resist fungal infections such as Candida albicans. Moreover, Aloe vera is considered as immunomodulatory agent and regulate inflammatory responses. In this study, twenty Balb/c mice were divided into five groups: four groups of infected mice with Candida albicans treated with different doses of Aloe vera extract and one healthy control group. Then, macrophage vital activity was measured by NBT assay. Nitric Oxide (NO) production as representative of macrophage activity was assayed by MTT test. Tumor Necrosis Factor alpha (TNF-α) and Interleukin-12 (IL-12) cytokines were measured by ELISA assay. Based on our study results, macrophage vital activity and NO production decreased significantly. However, TNF-α and IL-12 cytokines increased significantly in mice model infected by Candida albicans. Aloe vera extract could enhance macrophage activity through increase in TNF-α and IL-12 cytokines in Candida albicans infections. Therefore, Aloe vera could stimulate innate immune responses to eliminate Candida albicans.

Pulmonary complications are one of the most important long-term sulfur mustard (SM) exposure that chemical victims are suffering for years. IL-21 is one of the important cytokines contributing in chronic pulmonary inflammatory diseases. In this study, the serum and sputum levels of IL-21 and their correlations with pulmonary complications was evaluated 27 years after sulfur mustard exposure.
Final sample size was 475 (350 men and 125 women) SM exposed and 150 (100 men and 50 women from Rabat) unexposed controls. The age span of volunteers was 27-67 years.
There was no significant different between exposed and control groups in serum and sputum levels of IL-21, but the serum level of IL-21 showed a significant correlation with spirometry parameter (FEV1/FVC) in SM exposed group was observed.
The affected serum and sputum levels of IL-21 by sulfur mustard exposure were not variable, but there was a significant negative correlation between serum level of IL-21and FEV1/FVC in SM exposed group.

Matrix metalloproteinases (MMPs) are a family of proteinases and have the vigorous capacity to degrade all parts of the extracellular matrix. MMP enzymes strongly participate in physiological processes such as normal tissue remodeling and wound healing and in pathology of pulmonary diseases. They are released in response to environmental stimuli such as toxins and regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). Sulfur mustard (SM) is a chemical toxic which can cause severe permanent damages to lung tissues. The aim of this study was assessing the possible role of MMP-9 and TIMPs in SM-induced lung symptoms and signs in exposed patients 20 years after exposure.
Totally, 372 male volunteers with a history of SM exposure and 128 age- and sex-matched unexposed controls participated and were divided into three groups: normal, mild and moderate-severe. All participants underwent clinical evaluation and pulmonary function tests and serum concentrations of MMP-9 and its inhibitors were measured using the ELISA technique.
Serum level of MMP-9 was increased in the SM exposed group who had moderate-severe pulmonary complications compared with the SM exposed with normal lung (2.321 ± 2.836 vs. 1.546 ± 2.176, P = 0.001) while only the MMP-9/TIMP-4 complex was elevated in the SM exposed with normal lung individuals compared to its corresponding control group (85 ± 265 vs. 82 ± 222, P = 0.025). Although MMP-9 and its inhibitors did not show any correlation with spirometry findings, elevated circulating MMP-9 was detected in SM exposed patients with chronic chough and hemoptysis (P = 0.013 and P = 0.013 respectively).
High level of tissue disruption and remodeling mediators could influence lung structure in long-term after SM exposure. The correlation of clinical evaluation with these factors efficiently helps us to identify important effectors.