Inhibitory potency of the nettle lectin on neovascularization: a biomolecule for carbohydrate-mediated targeting of angiogenesis.

BACKGROUND: Current angiogenesis inhibitors target cellular vascularization processes, including proliferation, migration, and tube formation. In this study, we investigated the impact of Urtica dioica agglutinin (UDA) on the cellular vascularization process. METHODS AND RESULTS: Various concentrations of UDA were applied to normal (HUVEC, MCF-10 A, and HDF from humans, and L-929 from mice) and cancer (A431 and U87 from humans, and 4T1 from mice) cell lines at different times. The MTT, cell migration assay, differentiation of endothelial cells, expression of VEGF-A/VEGF-R2, and integrin α2 were evaluated. The MTT results demonstrated that UDA was non-toxic to normal cells while inhibiting the growth of neoplastic cells. The migratory capacity of HUVECs and U87 glioblastoma cells was inhibited by UDA in the wound repair model. This lectin inhibited HUVEC-induced vessel sprouting in the collagen-cytodex matrix. In addition, UDA treatment reduced VEGF-integrin cross-talk in HUVECs, confirming the anti-angiogenic activity of this molecule. CONCLUSIONS: Based on our findings, UDA may have an effect on cancer cell proliferation and vascularization events while causing minimal toxicity to normal cells via binding glyco-conjugates containing GlcNAc/man oligomers like EGFR. This is a blue clue for the angiogenesis-related therapeutic importance of UDA.

A review on human reproductive systems encountering with the severe acute respiratory syndrome coronavirus 2 infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the leading cause of the new deadly pneumonia named coronavirus disease 2019 (COVID-19) pandemic. This pathogen has different co-receptors on various tissues, resulting in vast pathophysiological circumstances. Here, we present a comprehensive narrative review focusing on the impact of SARS-CoV2 on human reproduction. Evidence-based literature revealed inconsistent results for this virus in the reproductive organs of patients with COVID-19, even in the critical phase. Conversely, numerous satisfactory data represented those different reproductive activities, from gametogenesis to pregnancy, can be targeted by SARS-CoV2. The severity of COVID-19 depends on the differential expression of the host cellular components required to enter SARS-CoV2. The cytokine storm and oxidative stress coming out during COVID-19 are associated with complications in reproductive endocrinopathies. Men are naturally more susceptible to COVID-19, especially accompanied by orchitis and varicocele. Synergistically the interaction of SARS-CoV2 and female reproductive failures (polycystic ovary syndrome and endometriosis) increases the susceptibility to COVID-19. Thus, pharmaceutical interventions that ameliorate the complications in individuals with reproductive disorders can be helpful to achieve good outcomes in assisted reproductive techniques. Soon, an increase in the infertility rate will likely be an overall impact of SARS-CoV2 in patients who recovered from COVID-19.

Effects of Urtica dioica agglutinin on glycotargeting of the vasculature: an in ovo study on chicken embryo.

The angiogenesis process is a pivotal cellular process involved in both developmental and pathological circumstances. In this study we investigated effect of Urtica dioica agglutinin (UDA), as an unusual phyto-lectin from the chitin-binding protein family, on the angiogenesis of chicken embryos. The UDA was extracted from plant rhizomes and purified by affinity chromatography column. The activity of this lectin was assayed by hemagglutination test on the human RBCs. Anti-angiogenic effect of UDA on the extra-embryonic layer of the chick egg was studied in the different concentrations. Our results showed that the minimum concentration of UDA for agglutination were 48.00 and 15.00 µg mL-1 in macro- and microscopic studies, respectively. Because the number and length of the vessels were dramatically decreased at 100 µg kg-1 of UDA, the lectin had an inhibitory effect on angiogenesis of the embryonic vasculature of the chick. We concluded that UDA might target the vascularization events through binding to GlcNAc-conjugates. More investigations are needed to clarify the angiogenesis-related therapeutic roles of this interesting biomolecule.

Randomized controlled trial of astaxanthin impacts on antioxidant status and assisted reproductive technology outcomes in women with polycystic ovarian syndrome.

PURPOSE: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women, is typically accompanied by a defective oxidative defense system. Here, we investigated the effect of astaxanthin (AST) as a powerful antioxidant on the oxidative stress (OS) response and assisted reproductive technology (ART) outcomes in PCOS patients. METHODS: In this double-blind, randomized, placebo-controlled trial, PCOS patients were randomly assigned into two groups. The intervention group received 8 mg AST, and the control group received the placebo daily for 40 days. The primary outcomes were the serum and follicular fluid (FF) levels of the OS biomarkers and the expression levels of the specific genes and proteins in the oxidative stress response pathway. The secondary outcomes were considered ART outcomes. RESULTS: According to our findings, a 40-day course of AST supplementation led to significantly higher levels of serum CAT and TAC in the AST group compared to the placebo group. However, there were no significant intergroup differences in the serum MDA and SOD levels, as well as the FF levels of OS markers. The expression of Nrf2, HO-1, and NQ-1 was significantly increased in the granulosa cells (GCs) of the AST group. Moreover, the MII oocyte and high-quality embryo rate were significantly increased in the AST group compared to the placebo group. We found no significant intergroup difference in the chemical and clinical pregnancy rates. CONCLUSION: AST treatment has been shown to increase both serum TAC levels and activation of the Nrf2 axis in PCOS patients' GCs. TRIAL REGISTRATION: ClincialTrials.gov Identifier: NCT03991286.

Antioxidant supplementations ameliorate PCOS complications: a review of RCTs and insights into the underlying mechanisms.

Polycystic ovary syndrome (PCOS) is one of the most important gynecological disorders of women in the age of reproduction. Different hormonal and inflammatory cross-talks may play in the appearance of its eventual complications as a leading cause of infertility. Excessive production of reactive oxygen species over the power of the antioxidant system as oxidative stress is known to contribute to a variety of diseases like PCOS. Thus, the utilization of antioxidants can be efficient in preventing or assistant in treating these diseases. In this review, we describe the clinical trial studies that have examined the efficiency of antioxidant strategies against PCOS and the possible underlying mechanisms. The investigations presented here lead us to consider that targeting oxidative stress pathways is probably a powerful promising therapeutic approach towards PCOS. There is preparatory evidence of the effectiveness of antioxidant interventions in ameliorating some of the PCOS complications, including metabolic and hormonal disorders. Due to limited data and relatively few clinical trials, many of these interventions need further investigation before they can be considered effective agents for routine clinical use.

Computational study of putative functional variants in human kisspeptin.

Non-synonymous single nucleotide polymorphisms (nsSNPs) are a type of genetic mutations that result in amino acid substitution of the encoded proteins that may potentially affect its function and phenotype. An In Silico assay has been carried out by using bioinformatics prediction tools to identify nsSNPs which are responsible for important disorders in human kisspeptin (KISS1) gene. In this study, for the first time, KISS1 amino acid changes were discovered by tBlastn for EST database. A list of nsSNPs in human KISS1 gene from dbSNP, dbEST and UniProt databases were prepared. Computational analysis was performed using SIFT (Sorting Intolerant From Tolerant) and PolyPhen (Polymorphism Phenotyping) programs. Of the total 92 nsSNPs, 20 were found to be damaged by both servers. Six nsSNPs (P97L, G122R, W114C, R92C, R120H and N115K) are predicted with the highest damaging scores (SIFT = 0, PolyPhen = 1). These intolerant changes may suggest their functional significance in critical regions which may affect the function and stability of KISS1 protein. Identifying these nsSNPs among the thousands of them make an opportunity to screen only those predicted deleterious by programs.

Immunomodulatory properties of mesenchymal stem cells: cytokines and factors.

Mesenchymal stem cells (MSCs) are defined as undifferentiated cells that are capable of self renewal and differentiation into several cell types such as chondrocyte, adipocyte, osteocyte, myocyte, hepatocyte, and neuron-like cells. MSC can be isolated from bone marrow, umbilical cord blood, adipose tissue, placenta, periosteum, trabecular bone, synovium, skeletal muscle, and deciduous teeth. Immunomodulatory of MSCs is one of the important issues nowadays, because this aspect can be clinically applied for graft-versus-host and autoimmune diseases. In this review, we tried to discuss in detail about cytokines and factors such as members of the transforming growth factor superfamily (transforming growth factor-ß), hepatic growth factors (HGF), prostaglandin E2 (PGE2), IL-10, indolamine 2,3-dioxygenase (IDO), nitric oxide (NO), heme oxygenase-1 (HO-1), and human leukocyte antigen-G (HLA-G) that are involved in immunomodulatory of MSCs.