Iranian Biomedical Journal
Volume:24 Issue: 5, Sep 2020

Precise regulation of signal transduction pathways is crucial for normal animal development and for maintaining cellular and tissue homeostasis in adults. The Wnt/Frizzled-mediated signaling includes canonical and non-canonical signal transduction pathways. Upregulation or downregulation of the canonical Wnt-signaling (or the Wnt/β-Catenin signal transduction) leads to a variety of human diseases, including many human cancers, neurodegenerative, skin, bone and heart deficiencies. Therefore, Wnt/β-Catenin signal transduction is a potential clinical target for the treatment of not only human cancers but also some other human chronic diseases. Here, some recent results including the results from my laboratory highlighting the role of Wnt/β-Catenin signal transduction in human cancers will be reviewed. After a brief overview on canonical Wnt signaling and introducing some critical β-Catenin/TCF-target genes, the interaction of canonical Wnt signaling with some common human cancers will be discussed. Finally, the different segments of this signaling pathway, which have been considered as targets for clinical purposes, will be discussed.

Rabies constantly kills 59,000 people annually, mostly in Asia and Africa. Rabies, which is responsible for 99% of human rabies cases, is totally preventable by standard vaccinations. In 2015, a global call for action was made by the World Health Organization, World Organization for Animal Health, Food and Agriculture Organization of the United Nations, and the Global Alliance for Rabies Control to join forces toward the elimination of dog-transmitted human rabies by the year 2030. All the tools and protocols to reach that target are readily available, and the feasibility of dog rabies elimination has been proven. Countries should drive the changes needed to engage into this global movement. Certainly, countries in the Eastern Mediterranean Region require taking more critical steps to reach the rabies elimination target by 2030. The international awareness campaign of the World Rabies Day is an excellent occasion to assess challenges and opportunities toward rabies elimination.

 IBD is a chronic inflammatory condition associated with damage to the intestinal mucosal barrier. Supplementation of yacon tubers has been known to give positive effect in intestinal health. Therefore, we conducted the study to investigate the effect of yacon tuber powder on Th1 activation pathway by evaluating IFN-γ levels and the number of goblet cells in the colon of colitis mouse models.

Thirty BALB/c mice were divided into five groups: 1, control group (G1) and 2-5, TNBS-induced colitis groups (GII-GV). Yacon powder was given to three of the TNBS-induced colitis groups with the doses of 0.165 g/30 g BW (GIII), 0.331 g/30 g BW (GIV), and 0.662 g/30 g BW (GV) for 14 days. IFN-γ levels were assessed using ELISA, while number of goblet cells was calculated based on histological observation.

Significantly lower IFN-γ levels was observed in GV compared to colitis group (GII) (p = 0.007). GV also showed significantly higher number of goblet cells per 100 epithelial cells in 20 crypts (p = 0,000) than GII.

The administration of yacon powder at a dose of 0.662 g/30 g BW could decrease IFN-γ levels and improve the healing of intestinal mucosa in colitis mouse models by increasing the number of goblet cells.

Previous data have shown the tumorigenicity roles of HDAC8 in breast cancer. More recently, the oncogenic effects of this molecule have been revealed in TNBC. The present study aimed to determine the diagnostic value of HDAC8 for the differentiation of TNBC from nTNBC tumors.

A total of 50 cancerous and normal adjacent tumor specimens were obtained, and the clinical and pathological findings of studied subjects were recorded. The expression of HDAC8 gene was determined by qRT-PCR. Also, immunohistochemical staining was performed on tissue samples.

Our results showed that the expression of HDAC8 in breast cancer tissues was significantly higher than the normal adjacent tissues (p = 0.0011). HDAC8 expression was also observed to be higher in TNBC patients than nTNBC group (p = 0.0013). In addition, in the TNBC group, there was a significant association between the HDAC8 overexpression and tumor characteristics, including tumor size (p = 0.039), lymphatic invasion (p = 0.01), tumor grade (p = 0.02), and perineural invasion (p < 0.05). The cut-off value was fixed at 0.6279 r.u., and the corresponding sensitivity and specificity were found to be 73.91% and 70.37%, respectively.

According to the findings, among the other markers, HDAC8 oncogene may be used as a potential tumor marker in diagnosis of TNBC tumors.

Vitamin D insufficiency and deficiency can be associated with adverse effects on fetus and pregnancy outcomes. This study aimed at evaluating the effect of 1,25VitD3 on specific transcription factor and markers of Tregs and Th17 cells in the PBMCs of women with URPL as a case group and the PBMCs of healthy women as a control group.

Samples from 20 non-pregnant patients with a history of URPL were compared to 20 normal non-pregnant women. PBMCs were divided into three wells for each subject in the presence of 1,25VitD3 (50 nM, for 16 hours), PHA (10 µM; positive control) and without any treatment (negative control). By Real-time PCR (Taqman assay), specific transcription factors of Tregs and Th17 cells, FOXP3, ROR-γt, GITR, and CTLA-4 mRNA expressions in two groups were measured.

FOXP3/ROR-γt mRNA expression in PBMCs decreased significantly in women experiencing URPL compared to the control group (p = 0.0001). Although 1,25VitD3 (50 nM) increased FOXP3 gene expression (p = 0.0001), it did not significantly affect ROR-γt gene expression. 1,25VitD3 treatment significantly increased FOXP3/ROR-γt mRNA expression from baseline in the PBMCs of the fetal loss group compared to that of the control group (p = 0.01). The 1,25VitD3 also increased GITR gene expression (p = 0.017) in the PBMCs of URPL women compared to the controls.

Vitamin D deficiency may be a contributor to recurrent pregnancy loss and suggests that the supplementation of women with Vitamin D pre-pregnancy may be protective against URPL via affecting Tregs signature genes, FOXP3 and GITR.

Neuropathic pain due to damage to the peripheral nerve has influenced millions of people living all over the world. It has been shown that paroxetine can relieve neuropathic pain. Recently, the role of some proteins like BDNF, GABAA receptor, and KCC2 transporter in the occurrence of neuropathic pain has been documented. In the current study, the expression of these proteins affected by paroxetine was evaluated.

Male Wistar rats were allocated into two main groups ofpre- and post-injury. Rats in each main group received paroxetine before nerve injury and at day seven after nerve damage till day 14, respectively. The lumbar spinal cord of animals was extracted to assess the expression of target genes and proteins.

In the preventive study, paroxetine decreased BDNF and increased KCC2 and GABAA gene and protein expression, while in the post-injury paradigm, it decreased BDNF and increased KCC2 genes and protein expression. In this regard, an increase in the protein expression of GABAA was observed.

It seems that paroxetine with a change in the expression of three significant proteins involved in neuropathic pain could attenuate this type of chronic pain.

The Peucedanum species have many pharmacological effects due to the presence of coumarins, flavonoids, phenolic compounds, and essential fatty acids in these species. In this study, for the first time, the anticancer activity of Peucedanum chenur methanolic extract via the induction of apoptosis and inhibition of invasion in HCT-116 human colon cancer cells was investigated.

 P. chenur methanolic extract effect on HCT-116 cells viability and antioxidant activity were evaluated using MTT assay, DPPH, and iron chelating tests, respectively. Changes in mRNA expression level in a panel of relevant genes were assessed by the quantitative real-time PCR. Also, apoptosis was assessed by cell cycle analysis and Annexin V/PI method, and the effect on cell migration was tested using scratch test.

P. chenur methanolic extract increased significantly the expression of BAX while decreased the expression of BCL-2, AKT1, FAK, RhoA, and MMP genes compared to the control group. BAX/BCL-2 ratio and apoptosis elevated, whereas cell migration reduced significantly. Besides, our extract showed an appropriate antioxidant activity.

 P. chenur may be introduced as a new chemopreventive agent in medicine due to its notable power in terms of induction of apoptosis and inhibition of invasion.

The Candida albicans is one of the most important global opportunistic pathogens, and the incidence of candidiasis has increased over the past few decades. Despite the established role of skin in defense against fungal invasion, little has been documented about the pathogenesis of Candida species when changing from normal flora to pathogens of vaginal and gastrointestinal epithelia. This study was carried out to determine in vivo and in vitro pathogenesis of clinical C. albicans strains isolated from skin lesions

In this study, association of in vivo and in vitro pathogenesis of C. albicans isolates with different evolutionary origins was investigated. Oral and systemic experimental candidiasis was established in BALB/C mice. The expression levels of secreted aspartyl proteinases (SAP1-3 genes), morphological transformation, and biofilm-forming ability of C. albicans were evaluated.

All the strains showed in vitro and in vivo pathogenicity by various extents. The SAP1, SAP2 and SAP3 genes were expressed in 50%, 100%, and 75% of the strains, respectively. The biofilm formation ability was negative in 12% of the strains, while it was considerable in 38% of the strains. Fifty percent of the strains had no phospholipase activity, and no one demonstrated high level of this pathogenesis factor. Relatively all the strains had very low potency to form pseudohyphae.

Our findings demonstrated that Candida albicans strains isolated from cutaneous candidiasis were able to cause oral and systemic infections in mice, so they could be considered as the potential agents of life-threatening nosocomial candidiasis in susceptible population.

Any irregularities in self-renewal/differentiation balance in endometriotic MSCs can change their fate and function, resulting in endometriosis development. This study aimed to evaluate the expression of OCT4 transcripts (OCT4A, OCT4B, and OCT4B1), SOX2, and NANOG in endometriotic MSCs to show their aberrant expression and to support self-renewal/differentiation imbalance in these cells.

MSCs were isolated from three endometriotic and three normal endometrium samples and characterized and analyzed for the expressions of OCT4A, OCT4B, OCT4B1, SOX2, and NANOG using the qRT-PCR.

The expressions of OCT4 transcripts and NANOG increased significantly in endometriotic MSCs, whereas SOX2 expression did not show any significant difference.

Our findings provide further evidence for confirming the self-renewal/ differentiation imbalance in endometriotic MSCs, as the main underlying cause of endometriosis development. This study also paves the way for further research on endometriosis treatment by focusing on endometriotic
stem cells.