The impact of Hyssop (Hyssopus officinalis) extract on activation of endosomal toll like receptors and their downstream signaling pathways.

OBJECTIVES: From the ancient, medicinal benefits of Hyssop (Hyssopus officinalis L.) have been implicated for respiratory and digestive diseases despite the effects of Hyssop on viral infections have not been mechanistically investigated. In this study, we examined whether the Hyssop extract activated anti-viral innate immunity, as a sentinel for immune system, through activation of endosomal TLRs recognizing nucleic acids and their downstream signaling. The Hyssop herb extracts was prepared and co-cultured with healthy individual's peripheral blood mononuclear cells (PBMCs). After viability assay, gene expression levels of TLR3,7,8,9, as well as MyD88 and NF-κB, were evaluated in treated PBMCs using Real-time PCR. Next, the secretion level of immune related cytokines was quantified via ELISA. RESULTS: Post 24 h, 40 µg/ml of the extract significantly inhibited the viability of less than 50% of cells compared to the control and had a maximum effect on cellular function. The Hyssop-treated PBMCs demonstrated an elevated expression of endosomal TLRs genes, as well as MyD88 and NF-κB. Moreover, the release of INF-α and ß notably enhanced in cell culture supernatant, while the content of inflammatory cytokines remarkably diminished (P < 0.05). The Hyssop extract was capable of inducing antiviral innate immune responses so can be promising in antiviral drug strategies.

Effects of nanocurcumin supplementation on T-helper 17 cells inflammatory response in patients with Behcet's disease: a randomized controlled trial.

OBJECTIVE: Present research was performed to assess the effects of nanocurcumin supplementation on T-helper 17 (Th17) cells inflammatory response in patients with Behcet's disease (BD). METHODS: In this randomized double-blind, placebo-controlled trial, 36 BD subjects were randomly placed into two groups to take 80 mg/day nanocurcumin or placebo for eight weeks. Disease activity, frequency of Th17 cells and expression of related parameters including retinoic acid-related orphan receptor γ (RORγt) transcription factor messenger RNA (mRNA), related microRNAs (miRNAs) such as miRNA-155, miRNA-181, and miRNA-326 as well as proinflammatory cytokines including interleukin (IL)-17 and IL-23 were evaluated. RESULTS: Thirty-two patients (17 in the nanocurcumin and 15 in the placebo groups) completed the trial. Number of Th17 cells decreased significantly in the nanocurcumin group compared to baseline (p = .012) and placebo (p = .047). Moreover, RORγt, IL-17, IL-23, miRNA-155, miRNA-181, and miRNA-326 mRNA expression decreased significantly in the nanocurcumin group compared with baseline (p = .004, p = .009, p < .001, p < .001, p < .001, p < .001, respectively) and placebo (p = .002, p = .021, p = .006, p = .035, p < .001, p = .017, respectively). Significant reductions in IL-17 and IL-23 were seen in nanocurcumin group compared with baseline (p = .017 and p = .015) and placebo (p = .047 and p = .048, respectively). Significant reduction in disease activity was observed in nanocurcumin group compared with placebo group (p = .035). CONCLUSION: Nanocurcumin supplementation had favorable effects in improving inflammatory factors and disease activity in BD patients. Additional studies are warranted to suggest nanocurcumin as a safe complementary therapy in BD.HighlightsNanocurcumin supplementation decreased Th17 cells frequency significantly compared with baseline and placebo group.Nanocurcumin supplementation decreased mRNA expression of RORγt, IL-17, IL-23, miRNA-155, miRNA-181, and miRNA-326 significantly compared to baseline and placebo group.Nanocurcumin supplementation decreased cell supernatant IL-17 and IL-23 significantly compared to baseline and placebo group.Nanocurcumin supplementation decreased disease activity significantly compared to placebo group.

The Effects of Cholecalciferol Supplementation on FGF23 and α-Klotho in Hemodialysis Patients With Hypovitaminosis D: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Vitamin D-fibroblast growth factor-23 (FGF-23)-klotho forms an axis that takes part at least in cardiovascular complications in patients with chronic kidney disease. This study aimed to assess the effects of cholecalciferol supplementation on FGF23 and α-klotho in patients with hypovitaminosis D requiring hemodialysis. METHODS: In a single-center, parallel-arm, randomized, double-blind, placebo-controlled trial, 86 patients with hypovitaminosis D requiring hemodialysis were enrolled. The patients were randomized into 2 groups (n = 43 each) to receive either 50,000 IU of cholecalciferol or placebo every week for 12 weeks. Accordingly, the serum levels of FGF23 and klotho were measured by ELISA and compared between both groups. RESULTS: Serum 25OH(D) levels increased in participants who received cholecalciferol supplementation compared with participants who received placebo (P = .006). In addition, serum FGF23 decreased and α-klotho levels increased in the supplemented group compared with placebo. However, the before-after differences between cholecalciferol supplement and placebo were significant only for α-klotho (P = .035). These effects were not accompanied by changes in the levels of phosphate, total and ionized calcium, and intact parathyroid hormone. CONCLUSION: Cholecalciferol supplementation of 50,000 IU for 12 weeks increases α-klotho levels in the serum of kidney failure patients undergoing hemodialysis. This may suggest that patients receiving maintenance hemodialysis can benefit from using cholecalciferol supplementation and increase in serum α-klotho levels.

Nanocurcumin supplementation ameliorates Behcet's disease by modulating regulatory T cells: A randomized, double-blind, placebo-controlled trial.

Current research was designed to assess the effects of nanocurcumin supplementation on regulatory T (Treg) cells frequency and function in Behçet's disease (BD). In this randomized double-masked, placebo-controlled trial, 36 BD subjects were randomly put into two groups to take one 80 mg nanocurcumin capsule or placebo daily for 8 weeks. Before and after trial, disease activity, Treg cells frequency and expression of related immunologic parameters including forkhead box protein P3 (Foxp3) transcription factor messenger RNA (mRNA) and microRNAs (miRNAs) such as miRNA-25 and miRNA-106b as well as cytokines including transforming growth factor (TGF)-ß and interleukin (IL)-10 were studied. Thirty-two patients (17 in the nanocurcumin and 15 in the placebo groups) completed the trial. Treg cells frequency increased significantly in the nanocurcumin group compared with baseline (P < 0.001) and placebo group (P < 0.001). Moreover, FoxP3, TGF-ß, IL-10, miRNA-25, and miRNA-106b mRNA expression levels increased considerably in the nanocurcumin group compared to baseline (P < 0.001) and placebo group (P < 0.001, P < 0.001, P = 0.025, P = 0.011, and P < 0.001, respectively). Significant increases in serum TGF-ß and IL-10 were seen in nanocurcumin group compared with baseline (P < 0.001) and placebo group (P = 0.001 and P < 0.001, respectively). Significant decrease in disease activity was found in nanocurcumin group compared with placebo group (P = 0.044). Our study provided a promising view for desirable effects of nanocurcumin supplementation in improving immunological parameters and disease activity in BD.

Association of Hippo Signalling Pathway with Epigenetic Changes in Cancer Cells and Therapeutic Approaches: A Review.

Hippo signalling pathway that is evolutionarily conserved affects diver's pathology and physiology processes, including tissue repair, wound healing, tissue size and tissue regeneration. Epigenetic changes are post-translational modifications in DNA proteins and histones. Epigenetic changes including histone acetylation and deacetylation, miRNAs dysregulation, and aberrant DNA methylation, inflammatory genes actives abnormal in Hippo signaling pathway. Using some treatments, including Histone Deacetylases (HDACs), herbal composition, siRNAs and long non-coding RNA (lncRNA) for suppressing cancer cells by targeting Hippo pathways, may open new views in cancer target therapy fields. The aim of this review study is firstly to demonstrate the importance of Hippo signalling and its association with epigenetic changes in cancer and then to demonstrate progress in targeting Hippo signalling in cancer therapy.

Berberine: A novel therapeutic strategy for cancer.

Cancer, even currently, is one of the main reasons for mortality and morbidity, worldwide. In recent years, a great deal of effort has been made to find efficient therapeutic strategies for cancer, however, particularly with regards to side effects and the possibility of complete remission. Berberine (BBR) is a nature-driven phytochemical component originated from different plant groups such as Berberis vulgaris, Berberis aquifolium, and Berberis aristata. BBR is a well-known nutraceutical because of its wide range of pharmacological activities including anti-inflammatory, antidiabetic, antibacterial, antiparasitic, antidiarrheal, antihypertensive, hypolipidemic, and fungicide. In addition, it exhibits inhibitory effects on multiple types of cancers. In this review, we have elaborated on the anticancer effects of BBR through the regulation of different molecular pathways such as: inducing apoptosis, autophagy, arresting cell cycle, and inhibiting metastasis and invasion.

Intrauterine administration of autologous hCG- activated peripheral blood mononuclear cells improves pregnancy outcomes in patients with recurrent implantation failure; A double-blind, randomized control trial study.

We aimed to investigate the effect of intrauterine administration of autologous hCG-activated PBMCs in RIF women with low Th-17/Treg cell ratio. 248 women with a history of implantation failure volunteered to receive PBMC-therapy. After immunologic consultation and doing flow cytometry analysis, 100 women with at least three IVF/ET failure who had low Th-17/Treg ratio in comparison with healthy control were enrolled in this study. These 100 patients were randomly divided into two groups as PBMC receiving (n = 50) and controls (n = 50). Then PBMCs were obtained from patients and treated with hCG for 48 h. Afterward, PBMCs were administered into the uterine cavity of the patient in the study group, two days before ET. The concentration of inflammatory cytokines was examined in the supernatant of cultured PBMCs after 2, 24, and 48 h of incubation using the ELISA method. The frequency of Th-17, Treg, and the Th-17/Treg ratio was significantly lower in RIF women than the healthy controls (P < 0.0001). The secretion of inflammatory cytokines was significantly higher after 48 h compared to 2 and 24 h (P < 0.0001). The pregnancy and live birth rate were significantly increased in women undergoing the PBMC-therapy compared to control (PBS-injecting) group (P = 0.032 and P = 0.047, respectively). The miscarriage rate was considerably lower in PBMC-therapy group (P = 0.029). Our findings suggest that intrauterine administration of autologous in vitro hCG-activated PBMCs improves pregnancy outcomes in patients with at least three IVF/ET failures.