Immunoregulation
Volume:7 Issue: 1, Summer 2024

Intrauterine adhesions (IUAs), also known as Asherman syndrome, is a pathological condition characterized by the development of fibrous scar tissue within the uterine cavity, leading to menstrual abnormalities, infertility, and recurrent pregnancy loss. Current treatment options for IUAs are limited and often associated with suboptimal outcomes. In recent years, mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs) have emerged as potential therapeutic tools for various tissue injuries and disorders. MSCs play an important role in regeneration and repair and can differentiate into several lineages. These cells can be harvested from various sources, such as bone marrow, umbilical cord, adipose tissue, peripheral blood, and placenta. EVs are small membrane-bound vesicles containing a diverse cargo of proteins, lipids, and nucleic acids, which can be transferred to target cells to modulate their biological functions. Evidence suggests that EVs possess therapeutic properties similar to their parent cells but without the risks associated with cell-based therapies. Studies have demonstrated that EVs, by multiple pathways and mechanisms, can promote endometrial repair, reduce fibrosis, and restore normal uterine function in animal models of IUAs. Understanding the therapeutic effects of MSCs-derived EVs on IUAs could pave the way for developing novel and minimally invasive treatment options for this challenging condition. This review provides an overview of the current knowledge regarding the therapeutic potential of different sources of MSC-EVs in treating IUAs in preclinical and in vitro studies.

Marjoram is an herbal plant with different medicinal effects. This study evaluates its impact on enzymatic antioxidant status, growth performance, intestinal mucosa morphology, and pulmonary hypertensive response in cold-induced pulmonary hypertensive chickens. 

Broiler chicks were reared for 35 days under cold stress and treated with 0.05% vitamin C (positive control) and 0 (control), 0.1%, or 0.2% marjoram extracts. Serum malondialdehyde (MDA) and activity of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD) were assayed on day 35. Meanwhile, gene expression of these enzymes was evaluated in the duodenum.

The right ventricle to total ventricles (RV:TV) ratio was lower in all treatments of chickens than control (P<0.05). The feed conversion ratio was only decreased in the chickens fed marjoram-0.2%. Lipid peroxidation was reduced in all groups, while the CAT activity was increased in the marjoram-0.2% group compared to the control (P<0.05). In the lung, SOD, CAT, and  GPX transcripts were decreased in the marjoram-0.2% group compared to the control (P<0.05). In the right ventricle of the heart, SOD and CAT transcripts were increased in the marjoram-0.2% group compared to other groups of chickens, whereas GPX transcript was decreased (P<0.05). In comparison to the control, the chickens fed vitamin C and marjoram had longer duodenal villus and more surface area, and their villus lamina propria was thicker (P<0.05). 

Supplementation of marjoram could modulate pulmonary hypertensive response and ameliorate intestinal morphology through its antioxidant effects.

Pulmonary hypertension syndrome (PHS) in broiler chickens is exacerbated by cold stress, leading to physiological responses that can adversely affect cardiac health. This study investigates the relationship between heart telomere length and lipid peroxidation in chickens experiencing PHS due to cold stress.

A total of 31-day-old male Ross 308 broiler chicks were divided into control and cold-stress (PHS) groups, with the latter exposed to decreasing temperatures to induce PHS. At 21 and 42 days of age, we assessed the right ventricular to total ventricular (RV:TV) ratio, relative heart telomere length through real-time quantitative PCR, and serum malondialdehyde (MDA) levels as a marker of lipid peroxidation.

The RV:TV ratio was significantly higher in the PHS group at both 21 days and 42 days compared to controls. Relative telomere length was significantly reduced in the PHS group at 42 days (P<0.05), while MDA levels were elevated at this age (P<0.05). A negative correlation between telomere length and MDA levels was observed at 42 days (P<0.05). 

Cold stress-induced PHS in broiler chickens leads to increased oxidative stress, as evidenced by elevated MDA levels and reduced telomere length. The findings suggest that oxidative damage may accelerate telomere attrition, linking environmental stressors to cardiac dysfunction in poultry.

Considering that non-eosinophilic esophagitis eosinophilic gastrointestinal disorders (EGIDs) could mimic serious surgical conditions, including hypertrophic pyloric stenosis, intussusception, and bowel perforation, this study investigates these disorders as major causes of gastrointestinal surgery in children. 

Children who had undergone gastrointestinal surgery between March 2017 and March 2018 at Mofid Children’s Hospital in Tehran City, Iran, were randomly selected to perform a rigorous and complete re-evaluation of the pathology to determine the presence of eosinophils or eosinophil-related inflammation in the tissue samples collected after surgery. Traditional hematoxylin and eosin staining was used to quantify eosinophils and their footprints. Trichrome staining was also applied to measure the tissue fibrosis. 

A total of 72 pediatric patients with a median age of 2.5 years, suffering from constipation and abdominal pain were studied. The majority of patients were primarily diagnosed with Hirschsprung’s syndrome (38.9%), followed by imperforated anus (34.7%) and ileal atresia (16.7%). Among the studied patients ten (13.9%) were confirmed to have tissue eosinophilia, compatible with the conventional method of non-EoE-EGID diagnosis. More evidence supporting the presence of tissue eosinophils was infiltration of 1-26 eosinophils in the muscular and subserosal layers of more than 97% of samples, degranulated eosinophils and multi-nucleated cells in 6(8.3%) tissue samples, and different levels of tissue fibrosis in 37 patients (51.4%).

Non-EoE EGIDs should be considered in the context of severe relapsing gastrointestinal complications requiring urgent or emergent surgical interventions, particularly in subjects without a convenient response after surgery.

Given the significant zoonotic threat posed by Salmonella enterica serovar Dublin (S. Dublin) and its substantial impact on animal populations and public health, the objective of the present study was to assess the immunogenicity and protectivity of subcutaneous administration of Salmonella Dublin bacterin in a murine model. 

Specific pathogen-free female BALB/c mice were tested for Salmonella-free status, and housed in controlled conditions. A formalin-killed bacterin was prepared from a local isolate of S. Dublin using a well-established protocol, ensuring bacterial inactivation and safety. Groups 1 through 3 of mice were received, respectively, either phosphate buffered saline plus alum or a single dose of inactivated bacterins with and without alum adjuvant via subcutaneous route. Immune responses were evaluated through microagglutination, enzyme-linked immunosorbent assay, delayed-type hypersensitivity, interferon-gamma assays, and challenge with viable S. Dublin.

Microagglutination and enzyme-linked immunosorbent assay tests revealed alum-adjuvanted injection as the best method for stimulation of anti-S. Dublin antibodies production. The gamma interferon production and delayed hypersensitivity tests, crucial for cellular immunity, were also most elevated in mice injected with alum-adjuvanted S. Dublin bacterin. After the challenge with the live bacteria, the isolation rate of S. Dublin was significantly different (P=0.03) among the different groups but only mice injected with alum-adjuvanted showed a significant difference (P≤0.05) compared to the control group.

This study emphasizes the efficacy of alum as an adjuvant in inactivated S. Dublin vaccines. Insights gained from both humoral and cellular immune responses, provide valuable knowledge for the development of S. Dublin vaccination strategies.