Therapeutic Features of Mesenchymal Stem Cells and Human Amniotic Epithelial Cells in Multiple Sclerosis

Imbalance in immune responses plays an indispensable role in pathogenesis and development of multiple sclerosis (MS), as a neurodegenerative disorder. Current treatments are not always successful in preventing MS development and treating the disease. Stem cell-based cell therapy has provided a new window for treating neurodegenerative disorders. Stem cells can regulate the immune system and improve axonal remyelination. They can be isolated from different origins such as bone marrow, embryonic, neural, and adipose tissues. However, there is a challenge in choosing the best cell source for stem cell therapy. Mesenchymal stem cells (MSCs) derived from different origins have significant immunoregulatory impacts on different cells from the immune system. A growing body of evidence indicates that adipose tissue and umbilical cord can be a suitable source for obtaining MSCs. Moreover, human amniotic epithelial cell (hAEC), as a novel stem cell with immunoregulatory effects, regenerative effects, and low antigenicity, can be a candidate for MS treatment. This chapter discusses therapeutic impacts of MSCs and hAECs in MS disease

Function of MicroRNAs in Normal and Abnormal Ovarian Activities: A Review Focus on MicroRNA-21

Abstract:Some failures in ovary function, like folliculogenesis and oogenesis, can give rise to various infertility-associated problems, including polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). PCOS influences 8 to 20% of women; while POI occurs in at least 1% of all women. Regrettably, the current therapies for these diseaseshave not sufficiently been effective, and finding a suitable strategy is still a puzzle. One of the helpful strategies for managing and treating these disorders is understanding the contributing pathogenesis and mechanisms. Recently, it has been declared that abnormal expression of microRNAs (miRNAs), as a subset of non-coding RNAs, is involved in thepathogenesis of reproductive diseases. Among the miRNAs, the roles of miRNA-21 in the pathogenesis of PCOS and POI have been highlighted in some documents; hence, the purpose of this mini-review was to summarize the evidence in conjunction with the functions of this miRNA and other effective microRNAs in the normal or abnormal functions of the ovary (i.e., PCOS and POI) with a mechanistic insight

Predicting role of Myc-induced nuclear antigen 53 in determining the development and severity of systemic lupus erythematosus

IntroductionSystemic lupus erythematosus (SLE) as an autoimmune disease can relate to an imbalance between regulatory T cells (Tregs) and Th17 cells. Previous reports have shown that Myc-induced nuclear antigen (Mina) 53 protein is involved in the developments of Tregs and Th17 cells. Therefore, the current study focused on determining whether Mina53 level is correlated to the severity of SLE.MethodsThe blood samples were collected from 60 patients with SLE (30 cases with mild SLE and 30 cases with severe SLE) and 30 healthy subjects. The serum concentration of Mina53 was measured using enzyme-linked immunosorbent assay (ELISA). The expression of Mina53 gene was assessed using real-time PCR method after extracting RNA from isolated peripheral blood mononuclear cells and synthesizing cDNA.ResultsPatients with SLE showed significant increases in the serum level and gene expression of Mina53 compared to healthy subjects (P<0.001). Furthermore, serum level and gene expression of Mina53 showed significant effects on SLE disease and its severity (P<0.01). There was the highest sensitivity and maximum specificity in the cut-off point of Mina53 serum level equal to 125.4 (area under the curve (AUC)=0.951) and Mina53 expression level equal to 8.5 (AUC=0.88) for SLE diagnosis. The cut-off point of Mina53 serum level equal to 139.5 (AUC=0.854) and the cut-off point of Mina53 expression level equal to 8.5 (AUC=0.788) had the highest sensitivity and maximum specificity determining severe forms of SLE.DiscussionOur results showed that the changes in serum and expression levels of Mina53 have significant effects on SLE disease and its severity. These levels may be considered as diagnostic and predictive markers for SLE

Association Between Helicobacter Pylori Infection and Seronegative Neuromyelitis Optica Spectrum Disorder

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease in the central nervous system. Association between NMOSD and Helicobacter pylori (H. pylori) infection has been investigated, but few studies have assessed the relationship between H. pylori and seronegative AQP4-Ab NMOSD. Objectives: This study aimed to survey the association between H. pylori infection and NMOSD patients with seronegative AQP4-Ab status, as well as the possible relationship between the presence of H. pylori and clinical characteristics. Materials & Methods: This cross-sectional study was carried out in Kashani Hospital affiliated with the Isfahan University of Medical Sciences, Isfahan, Iran, from October 2017 to May 2019. A total of 35 consecutive seronegative AQP4-Ab NMOSD patients and 37 sex and age-matched healthy controls participated in the study. Demographic and clinical characteristics were obtained from all participants. We assessed participants’ seroprevalence of IgG and IgM antibodies against H. pylori. The Association of H. pylori with NMOSD was determined. Results: The frequency of IgG and IgM Ab H. pylori seropositivity in NMOSD patients was 22.9% and 40.0%, respectively. Among HC, 11(29.7%) and 20(54.1%) were positive for IgG and IgM Ab H. pylori. Although the rate of H. pylori IgG (OR=0.700, 95%, CI=0.243, 2.017, P=0.420) and IgM Ab (OR=0.567, 95%, CI=0.222, 1.444, P=0.233) seropositivity in NMOSD were lower than NMOSD, these differences were not statistically different. No clinical variables associated with H. pylori IgG and IgM seropositivity infection seropositivity. Conclusion: These findings show that possibly there is no relationship between H. pylori infection and seronegative AQP4-Ab NMOSD

Immunogenicity and safety of the BBIBP‐CorV vaccine in patients with autoimmune inflammatory rheumatic diseases undergoing immunosuppressive therapy in a monocentric cohort

Abstract Introduction Vaccination plays a fundamental role in mastering the COVID‐19 pandemic and protecting vulnerable groups. Persons with autoimmune inflammatory rheumatic diseases (AIIRD) requiring immunosuppressive therapies are prioritized for vaccination. However, data concerning immunogenicity and safety of the BBIBP‐CorV vaccine in immunosuppressed patients are not found. This study presents data on the efficacy and safety of the BBIBP‐CorV vaccine in immunosuppressed patients compared to healthy controls. Methods Study population consisted of 100 healthy controls and 100 patients with AIIRD. Vaccination was performed according to national guidelines with the BBIBP‐CorV vaccine. SARS‐CoV‐2 neutralizing antibody titers were quantified by enzyme‐linked immunosorbent assay before initial vaccination and 1–3 months after secondary vaccination. Adverse events were assessed before study initiation and 7 days after the second dose. Disease activity was studied before entering the study and 3–8 weeks after the second dose. Results Vaccination‐induced positive immunogenic response rates and SARS‐CoV‐2 neutralizing antibody titers were significantly lower in the AIIRD patients than healthy subjects (p < .05). There are significant differences in neutralizing antibody titers among patients suffering from rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis, and ankylosing spondylitis (p < .01–.05). The rates of seropositive vaccine responses were similarly distributed across all diseases. Healthy and AIIRD individuals had a similar profile in adverse events. No significant difference was observed in SARS‐CoV‐2 antibody titers between subjects suffering from side effects and those who did not have. SARS‐CoV‐2 neutralizing antibody levels were significantly higher in subjects with a history of COVID‐19 infection than seronegative individuals (p < .01–0.05). Seropositive subjects had a significant increase in the percentage of vaccine‐related adverse events compared to seronegative persons (p < .05). Despite a minor change in the disease activity of patients with RA and SLE, disease activity indices were overall stable in the AIIRD patients. Conclusion These findings revealed that the BBIBP‐CorV vaccine is effective in the development of neutralizing antibodies in immunosuppressed patients without considerable reactogenicity or induction of disease flares

Method and key points for isolation of human amniotic epithelial cells with high yield, viability and purity

Abstract Objective Human amniotic epithelial cells (hAECs) which are isolated from the amniotic membrane have stem cell-like properties and immunomodulatory effects. Several protocols have been proposed for isolation of hAECs, nevertheless, there is no report concerning isolation of highly viable hAECs, with desirable yield, and without significant purity reduction. In the current study, a detailed protocol with some modification of previous ones is presented in which the amendments led to isolation of hAECs with high purity, yield and viability. Moreover, isolated hAECs were subjected to immuno-phenotyping and their physiological status was assessed using a proliferation assay. Results The average yield of obtained hAECs using the new modified method was 190 × 106 cells with a mean viability of 87%, with less than 1% contamination with mesenchymal stem cells (MSCs). The isolated cells were > 95% positive for the epithelial cell markers. The lowest initial plating efficiency of the cells was 80%. Freshly isolated hAECs had the ability to proliferate for 5–6 passages in a standard culture medium

The Therapeutic Potential of Common Herbal and Nano-Based Herbal Formulations against Ovarian Cancer: New Insight into the Current Evidence

Ovarian cancer (OCa) is characterized as one of the common reasons for cancer-associated death in women globally. This gynecological disorder is chiefly named the &ldquo;silent killer&rdquo; due to lacking an association between disease manifestations in the early stages and OCa. Because of the disease recurrence and resistance to common therapies, discovering an effective therapeutic way against the disease is a challenge. According to documents, some popular herbal formulations, such as curcumin, quercetin, and resveratrol, can serve as an anti-cancer agent through different mechanisms. However, these herbal products may be accompanied by some pharmacological limitations, such as poor bioavailability, instability, and weak water solubility. On the contrary, using nano-based material, e.g., nanoparticles (NPs), micelles, liposomes, can significantly solve these limitations. Therefore, in the present study, we will summarize the anti-cancer aspects of these herbal and-nano-based herbal formulations with a focus on their mechanisms against OCa

Toll-like receptor 4 activation on human amniotic epithelial cells is a risk factor for pregnancy loss

Background: Maternal–fetal tolerance plays a fundamental role in the maintenance of pregnancy. However, this immunological tolerance can be influenced by intrauterine infections. Human amniotic epithelial cells (hAECs) have immunomodulatory effects and respond to invading pathogens through expressing various toll-like receptors (TLRs). We hypothesize that bacteria or bacterial products affect the immunosuppressive effects of hAECs through TLR stimulation. Here, we investigated how a successful pregnancy can be threatened by TLR4 activation on hAECs on lipopolysaccharide (LPS) engagement. Materials and Methods: hAECs were isolated from the amniotic membrane received from six healthy pregnant women. The immunophenotyping of hAECs was studied by flow cytometry. The isolated hAECs (4 × 105 cells/ml) were cultured in 24-well plates in the presence or absence of LPS (5 μg/ml). After 24, 48, and 72 h of incubation, the culture supernatants of hAECs were collected, and the levels of interleukin-5 (IL-5), IL-6, IL-1β, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1), and prostaglandin E2 (PGE2) were measured by enzyme-linked immunosorbent assay. Results: TLR4 activation showed a stimulatory effect on TGF-β1 production of hAECs (P < 0.001–0.05). PGE2 production of LPS-stimulated hAECs was significantly increased (P < 0.01–0.05). Moreover, TLR4 could induce TNF-α and IL-1β production of hAECs (P < 0.0001–0.01), while this effect was not observed on IL-6 production of hAECs. The IL-5 was produced at a very low level in two culture supernatants of hAECs, in which its production was independent of LPS effect. Conclusion: TLR4 activation by bacterial components on hAECs may be a potential risk factor for pregnancy complications

The effect of lipopolysaccharide on the expression level of immunomodulatory and immunostimulatory factors of human amniotic epithelial cells

Abstract Objective Human amniotic epithelial cells (hAECs) are a novel source of stem cells and have immunomodulatory effects on both the innate and adoptive immune system. hAECs can differentiate into multiple cell lineages that make them a suitable cell source for regenerative medicine. These cells express multiple toll-like receptors (TLRs) and respond to various TLR ligands. This study aimed to evaluate the effect of lipopolysaccharide (LPS), a TLR4 ligand, on the level of immunomodulatory and immunostimulatory factors of hAECs. Results Our results indicated that LPS had the ability to up-regulate the expression of prostaglandin E2 synthase and transforming growth factor-beta1 in hAECs. However, there was no change in the level of interleukin-1beta, interleukin-6 and interleukin-10 in hAECs when were stimulated with LPS. In addition, we observed tumor necrosis factor-alpha was only expressed at very low level in some of hAECs samples which its expression was independent of the effects of LPS