Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a significant threat to global health. This virus affects the respiratory tract and usually leads to pneumonia in most patients and acute respiratory distress syndrome (ARDS) in 15% of cases. ARDS is one of the leading causes of death in patients with COVID-19 and is mainly triggered by elevated levels of pro-inflammatory cytokines, referred to as cytokine storm. Interleukins, such as interleukin-6 (1L-6), interleukin-1 (IL-1), interleukin-17 (IL-17), and tumor necrosis factor-alpha (TNF-α) play a very significant role in lung damage in ARDS patients through the impairments of the respiratory epithelium. Cytokine storm is defined as acute overproduction and uncontrolled release of pro-inflammatory markers, both locally and systemically. The eradication of COVID-19 is currently practically impossible, and there is no specific treatment for critically ill patients with COVID-19; however, suppressing the inflammatory response may be a possible strategy. In light of this, we review the efficacy of specific inhibitors of IL6, IL1, IL-17, and TNF-α for treating COVID-19-related infections to manage COVID-19 and improve the survival rate for patients suffering from severe conditions. Graphical Abstract

Placental growth factor (PlGF) is an angiogenic factor which belongs to vascular endothelial growth factor (VEGF) family. In addition to the angiogenic function of PlGF, in some conditions such as preeclampsia and early pregnancy losses, it can induce inflammatory reactions which could be accompanied with reduced angiogenesis. Hence, it is crucial to investigate inflammatory and angiogenic switching states and understand underlying mechanisms. PlGF is expressed in endometrium, placenta and trophoblast cells and is involved in maturation of uterine NK cells. Up-regulation of PlGF directs VEGF to VEGFR-2 and reinforces angiogenesis. However, when VEGF/VEGFR-2 signaling pathway is impaired, PlGF may shift to severe inflammation and cause tissue damages which could lead to early pregnancy losses. Downregulation of PlGF has also been reported in pregnancy complications. In this review, we discussed the role of PlGF in embryo implantation failure and early pregnancy loss and also possible mechanisms regarding the role of PlGF in angiogenic/inflammatory switching in early pregnancy losses. Furthermore, we summarized the effects of various compounds on PlGF expression and briefly talked about its therapeutic potential that may be an opportunity for prevention of pregnancy loss.

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Over the past few years, the cancer-related disease has had a high mortality rate and incidence worldwide, despite clinical advances in cancer treatment. The drugs used for cancer therapy, have high side effects in addition to the high cost. Subsequently, to reduce these side effects, many studies have suggested the use of natural bioactive compounds. Among these, which have recently attracted the attention of many researchers, quercetin has such properties. Quercetin, a plant flavonoid found in fresh fruits, vegetables and citrus fruits, has anti-cancer properties by inhibiting tumor proliferation, invasion, and tumor metastasis. Several studies have demonstrated the anti-cancer mechanism of quercetin, and these mechanisms are controlled through several signalling pathways within the cancer cell. Pathways involved in this process include apoptotic, p53, NF-κB, MAPK, JAK/STAT, PI3K/AKT, and Wnt/β-catenin pathways. In addition to regulating these pathways, quercetin controls the activity of oncogenic and tumor suppressor ncRNAs. Therefore, in this comprehensive review, we summarized the regulation of these signalling pathways by quercetin. The modulatory role of quercetin in the expression of various miRNAs has also been discussed. Understanding the basic anti-cancer mechanisms of these herbal compounds can help prevent and manage many types of cancer.

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Clinical oncologists need more reliable and non-invasive diagnostic and prognostic biomarkers to follow-up cancer patients. However, the existing biomarkers are often invasive and costly, emphasizing the need for the development of biomarkers to provide convenient and precise detection. Extracellular vesicles especially exosomes have recently been the focus of translational research to develop non-invasive and reliable biomarkers for several diseases such as cancers, suggesting as a valuable source of tumor markers. Exosomes are nano-sized extracellular vesicles secreted by various living cells that can be found in all body fluids including serum, urine, saliva, cerebrospinal fluid, and ascites. Different molecular and genetic contents of their origin such as nucleic acids, proteins, lipids, and glycans in a stable form make exosomes a promising approach for various cancers’ diagnoses, prediction, and follow-up in a minimally invasive manner. Since exosomes are used by cancer cells for intercellular communication, they play a critical role in the disease process, highlighting the importance of their use as clinically relevant biomarkers. However, regardless of the advantages that exosome-based diagnostics have, they suffer from problems regarding their isolation, detection, and characterization of their contents. This study reviews the history and biogenesis of exosomes and discusses non-coding RNAs (ncRNAs) and their potential as tumor markers in different types of cancer, with a focus on next generation sequencing (NGS) as a detection method. Moreover, the advantages and challenges associated with exosome-based diagnostics are also presented.

HLA-G is a nonclassical Class I major histocompatibility complex (MHC) gene. This gene has a limited protein alteration that is produced by alternative splicing and can be important in the preservation of pregnancy. Recent findings suggest that alteration in HLA-G gene expression can lead to pregnancy failure, such as recurrent pregnancy loss (RPL). As the promoter SNPs of the gene may impact the HLA-G expression levels, the study of these SNPs is very important. In this study, for the promoter region of HLA-G gene in the case group (100 women with a history of two or more repeated miscarriages) and the control group (100 women with at least two successful pregnancies), PCR reaction was performed. Thereafter, PCR products were sequenced and the results were compared between the two groups. The results showed that -1573T>C and -1746C>A SNPs in the promoter of the HLA-G gene associated with RPL. The outcome of the haplotype analysis also showed that the association of two haplotypes, including H1 (ATCCAGGTACGCAA) and H2 (CTTCGAGAACGCAG) with RPL, is significant. The results showed that H1 is associated with a decreased and H2 is associated with an increased risk of RPL. These results indicate the importance of the HLA-G promoter SNPs in the pregnancy outcome. But to reach a more definite conclusion, subsequent studies on 3' UTR and other positions with polymorphism in the 5' UTR regions larger samples are necessary.

Introduction An abnormal endometrial immune response is involved in the pathogenesis of repeated implantation failure (RIF), so we investigated the effectiveness of tacrolimus treatment on the endometrium of RIF patients. Materials and Methods Ten RIF patients with elevated T-helper 1/T-helper 2 (Th1/Th2) cell ratios were recruited into a clinical study. The expression of p53, leukemia inhibitory factor (LIF), interleukin (IL)-4, IL-10, IL-17, and interferon gamma (IFN-γ) in the endometrium of patients with and without tacrolimus treatment and the association of these factors with assisted reproductive technology (ART) outcomes were investigated. Results Tacrolimus significantly increased the expression of LIF, IL-10, and IL-17 and decreased the expression of IL-4, IFN-γ, and the IFN-γ/IL-10 ratio in RIF patients. Tacrolimus treatment resulted in an implantation rate of 40%, a clinical pregnancy rate of 50%, and a live birth rate of 35% in RIF patients with elevated Th1/Th2 ratios who had previously failed to become pregnant despite at least three transfers of embryos. We also found a significant positive correlation between IL-10 levels and the implantation rate. Conclusions Our findings suggest that RIF patients with a higher Th1/Th2 ratio could be candidates for tacrolimus therapy and that this immunosuppressive drug could be acting through upregulation of LIF, IL-10, and IL-17.