Nervous system disorders are one of the common problems that affect many people around the world every year. Regarding the beneficial effects of the probiotics on the gut and the gut-brain axis, their application along with current medications has been the subject of intense interest. Psychobiotics are a probiotic strain capable to affect the gut-brain axis. The effective role of Psychobiotics in several neurological disorders is documented. Consumption of the Psychobiotics containing nutrients has positive effects on the improvement of microbiota as well as alleviation of some symptoms of central nervous system (CNS) disorders. In the present study, the effects of probiotic strains on some CNS disorders in terms of controlling the disease symptoms were reviewed. Finding suggests that Psychobiotics can efficiently alleviate the symptoms of several CNS disorders such as autism spectrum disorders, Parkinson’s disease, multiple sclerosis, insomnia, depression, diabetic neuropathy, and anorexia nervosa. It can be concluded that functional foods containing psychotropic strains can help to improve mental health. Graphical Abstract

Abstractβ-Arrestins (βArrs) are intracellular signal regulating proteins. Their expression level varies in some cancers and they have a significant impact on cancer cell function. In general, the significance of βArrs in cancer research comes from studies examining GPCR signalling. Given the diversity of different GPCR signals in cancer cell regulation, contradictory results are inevitable regarding the role of βArrs. Our approach examines the direct influence of βArrs on cellular function and gene expression profiles by changing their expression levels in breast cancer cells, MDA-MB-231 and MDA-MB-468. Reducing expression of βArr1 or βArr2 tended to increase cell proliferation and invasion whereas increasing their expression levels inhibited them. The overexpression of βArrs caused cell cycle S-phase arrest and differential expression of cell cycle genes, CDC45, BUB1, CCNB1, CCNB2, CDKN2C and reduced HER3, IGF-1R, and Snail. Regarding to the clinical relevance of our results, low expression levels of βArr1 were inversely correlated with CDC45, BUB1, CCNB1, and CCNB2 genes compared to normal tissue samples while positively correlated with poorer prognosis in breast tumours. These results indicate that βArr1 and βArr2 are significantly involved in cell cycle and anticancer signalling pathways through their influence on cell cycle genes and HER3, IGF-1R, and Snail in TNBC cells.

Cetuximab is a monoclonal antibody developed to inhibit the binding of growth factors and the subsequent activation of epidermal growth factor receptor (EGFR). Triple-negative breast cancer (TNBC) is resistant to cetuximab treatment. The aim of the present study was to examine the partial agonistic properties of cetuximab, which not only blocks ligand binding, but also partially triggers EGFR activation, which may lead to cetuximab resistance in TNBC. The phosphorylation of growth factor receptors and their signalling pathways were evaluated by determining the phosphorylation of EGFR, insulin-like growth factor receptor (IGF-1R), vascular endothelial growth factor receptor (VEGFR)-2, Src kinase, phosphoinositide-3-kinase (PI3K), extracellular signal-regulated kinase (ERK1/2) and serine/threonine-specific protein kinase (Akt) and the degradation of EGFR, and by assessing the morphology and proliferation of MDA-MB-231 and MDA-MB-468 cells. Cetuximab treatment led to the phosphorylation of EGFR, VEGFR-2, IGF-1R and downstream signalling molecules, Src kinase and PI3K in these cells, as well as Akt in the MDA-MB-231 cells. The cetuximab-mediated phosphorylation of IGF-1R, VEGFR-2 and Akt was inhibited by the EGFR kinase inhibitor, AG1478, and the Src kinase inhibitor, PP2. Cetuximab treatment led to the degradation of EGFR. The cetuximab-induced phosphorylation and EGFR degradation were less prominent compared with those induced by EGF. Cetuximab partially inhibited EGF-mediated responses. Cetuximab, similar with EGF, altered cellular morphology in a serum-free medium. In both cell lines, the Src kinase inhibitor enhanced the cetuximab-induced anti-proliferative response. These results indicate that cetuximab exerts a partial agonistic effect on EGFR, which activates Src kinase and subsequently transactivates IGF-1R and VEGFR-2. This partial agonistic property is likely one of the mechanisms underlying the resistance of TNBC to cetuximab.

Triple negative breast cancer cell lines express high levels of β2-adrenergic receptor, which have a significant influence on the activity of extracellular signal‑regulated kinase (ERK)1/2. Therefore, it is important to understand the link between β2‑adrenergic receptor signaling and ERK1/2 activity in terms of cancer cell regulation and cancer progression. Although the molecular mechanisms are not completely clarified, β2‑adrenergic receptor stimulation appears to reduce the basal levels of phosphorylated (p)ERK1/2 in MDA‑MB‑231 breast cancer cells. The aim of the current study was to determine the mechanism of β2‑adrenergic receptor‑mediated ERK1/2 dephosphorylation by investigating the role of dual‑specificity phosphatase (DUSP)1/6 and protein phosphatase (PP)1/2, which are established regulators of ERK1/2 phosphorylation, in MDA‑MB‑231 and MDA‑MB‑468 breast cancer cell lines. (E)‑2‑benzylidene‑3‑(cyclohexyl​amino)‑2,3‑ dihydro‑1H‑inden‑1‑one (BCI) and calyculin A were employed as DUSP1/6 and PP1/PP2 inhibitors, respectively. Subsequently, the protein levels of DUSP1, PP1, pPP1, ERK1/2 and pERK1/2 were measured by western blot analysis. Cells were transfected with DUSP1 small interfering (si)RNA or PP1 siRNA to inhibit their expression. The results demonstrated that β2‑adrenergic receptor agonists led to the dephosphorylation of basal pERK1/2 in MDA‑MB‑231 and MDA‑MB‑468 cells. The DUSP1/6 inhibitor, BCI, and the PP1/PP2 inhibitor, calyculin A, antagonized the β2‑adrenergic receptor‑mediated dephosphorylation of ERK1/2. Furthermore, β2‑adrenergic receptor stimulation increased the protein expression level of DUSP1, with no effects on DUSP6, PP1 and PP2 expression, and enhanced the expression of the active form of PP1. Downregulation of the expression of DUSP1 or PP1 led to a decline in the β2‑adrenergic receptor‑mediated dephosphorylation of ERK1/2. The results of the present study indicate that β2‑adrenergic receptor‑mediated dephosphorylation of ERK1/2 may be associated with the activity of DUSP1 and PP1 in MDA‑MB‑231 and MDA‑MB‑468 triple negative breast cancer cell lines. The clinical importance of β2‑adrenergic receptor‑mediated inactivation of ERK1/2 as well as the activation of DUSP1 and PP1 should be carefully evaluated in future studies, particularly when β2‑adrenergic blockers are used in patients with triple negative breast cancer.

Background and Objectives: Phytotherapeutically, various herbal remedies, such as St. John’s wort oil, have been introduced as wound care options. Recently, Neem oil has been considered a herbal option for the management of superficial wounds. Wound care is a complex process that involves several factors including the patient, caregiver, and medications. Herbal combinations could be an alternative to the chemical counterparts in the wound care area. This report includes an investigation of the possible supportive impacts of the St. John’s wort and Neem oil containing ointment (W Cura G Plus ®) in the management of pressure ulcers (PUs) in three intensive care unit (ICU) patients. Materials and Methods: The ointment was administered to individuals once daily for 42 consecutive days. The status of individuals was macroscopically monitored by measuring the PU area and histopathological assessment of the tissue sections taken on the first and last days of wound treatment. Results: The outcomes of the macroscopic and histopathological techniques exhibited that St. John’s wort and Neem oil containing ointment provided a remarkable supportive impact on the patients that suffered from PUs in the ICUs. Conclusions: The combination of St. John’s wort and Neem oil could be suggested as an efficient active phytoconstituent for the management of PUs. The herbal ointments may be suggested as an alternative for the patients that have PUs in the ICUs.