جستجوی مقالات مرتبط با کلیدواژه « cathepsin d » در نشریات گروه « پزشکی »

Fasciolosis is a global parasitic disease caused by liver trematodes such as Fasciola hepatica, affecting various mammals, including sheep, goats, cattle, pigs, and humans worldwide. Cathepsin L (Cat L) found in the life stages of F. gigantica is associated with the pathology of the fluke. Given the detrimental impact of fasciolosis on animal health and production, along with reports of drug resistance and concerns regarding drug residues in animal products and the environment, there has been an increasing emphasis on developing a potent epitope-based vaccine to combat this infection.

The present study aimed at bioinformatically analyzing the characteristics of Cat L of F. gigantica newly encysted juvenile (FgNEJ) to identify potential epitopes for constructing an effective vaccine against the infection.

The Cat L of FgNEJ was analyzed using several reliable bioinformatics tools.

Analysis of the second structure of the Cat L amino acid sequence demonstrated that the alpha-helix, random coil, and extended strand ratios were 77 (23.62%), 164 (50.31%), and 85 (26.07%), respectively. Analysis of B-cell, T-cell, and MHC epitopes predicted on the sequence suggested Cat L of FgNEJ as an ideal target for vaccine design.

The current study introduces significant information on Cat L of FgNEJ, as well as some promising epitopes that can be used as strong candidates in studies involved in developing a vaccine against fasciolosis.

Recently, the role of sports training and medicinal plants in the expression of genes has been considered to prevent the progression of diseases. The purpose of this research was to investigate the role of weight training and oleander extract on interferon regulatory factor 8 (IRF8) and cathepsin S (CTSS) gene expression in the soleus muscle of Alzheimer's disease (AD) model mice.

Fifty-five male Wistar rats were randomly divided into 5 groups: healthy control group, AD control group, AD resistance training group, AD group with the supplement of Melilotus officinalis, and AD resistance training group + Melilotus officinalis supplement. Trimethyltin-induced AD was induced. In the resistance training protocol, a weight was attached to the tail of the rats, and they had to lift this weight on a ladder with 26 steps. Melilotus officinalis was injected intraperitoneally as a supplement for 6 weeks with a dose of 300 mmol/kg. Seventy-two hours after the last training session, the rats were anesthetized, and the hippocampal tissue was immediately extracted, frozen, and analyzed. A two-way analysis of variance was used to estimate the differences between groups in control and experimental AD mice.

There was a significant increase in the expression level of interferon-regulating factor 8 and cathepsin S genes in the AD group compared to the control group. The results of Bonferroni's post-hoc test showed that in the AD group + resistance training + Melilotus officinalis, a significant decrease was observed compared to the AD group (P≤0.05).

Resistance training and the Melilotus officinalis extract with antioxidant mechanisms can affect CTSS and IRF8 gene expression.

Cathepsin-D is a well-known protease that promotes invasion in tumoral lesions. Considering the cystic neoplasm nature of odontogenic keratocyst (OKC), the aim of this study was to compare the expression of cathepsin-D in this lesion with the unicystic ameloblastoma (UA) and orthokeratinized odontogenic cyst (OOC) for better understanding of its behavior.

In this descriptive-analytical study, we used paraffin blocks available in the archives of oral and maxillofacial pathology department of dental school (8 unicystic ameloblastoma (UA), 8 odontogenic keratocyst (OKC) and 8 orthokeratinized odontogenic cysts (OOC)) which they were stained immunohistochemically with cathepsin-D. Then, the samples were observed simultaneously by two oral pathologists for detection the intensity and pattern of epithelial and stromal cells staining. Data were analyzed by SPSS20 and Kruskal-Wallis, Mann-Whitney and Chi-square test (P<0.05).

The staining intensity of the epithelial cells of UA group was significantly more than OOC and OKC (P=0.02). The staining intensity of the stromal cells of UA was more than the other two groups, although this difference was not statistically significant (P=0.32). The pattern of cell staining in epithelium and stroma did not show any significant difference between the three groups in this study (P=0.15, 0.22).

The results of this study regarding the intensity expression of cathepsin-D in these three odontogenic lesions could be considered as a probable evidence for the new odontogenic lesions classification (WHO2017) in terms of reintroducing OKC as an odontogenic cyst. If this idea is rejected, it seems that cathepsin-D expression is not associated with the invasive behavior of this cyst, and further investigation of other markers in the epithelium and stroma simultaneously is suggested for a better understanding of its biological nature.

Juvenile neuronal ceroid lipofuscinosis (JNCL), one of the most frequent forms of the NCL storage diseases, is known to be caused by loss-of-function mutations in ceroid-lipofuscinosis neuronal protein 3 (CLN3), but its cell function has not been fully elucidated. We previously reported increased lysosomal pH in CLN3 deficient cells. In the present study, we analysed the consequences of this effect in the endo-lysosomal pathways in CLN3 cells.

The present study investigated different endo-lysosomal pathways in control, CLN2, CLN3 human skin fibroblasts under high and low proteolysis conditions. Cell surface biotinylation after EGF (2 ng/mL) stimulation, EGF phosphorylation (Tyr-845), retromer and cation-independent mannose-6-phosphate receptor (CI-MPR) levels and stability, EGF degradation pathways and cathepsin L and D levels were analysed by western blots. Caveolae mediated endocytosis was analysed by flow cytometry. CIMPR subcellular localization was ascertained by immunocytochemistry, confocal microscopy and further image analysis.

Whereas caveolae-mediated endocytosis was not affected in CLN3 cells, clathrin-mediated epidermal growth factor (EGF) internalization was reduced, along with EGF receptor (EGFR) phosphorylation. In addition, cell surface EGFR levels and recycling to the cell membrane were increased. EGFR lysosomal degradation was impaired and our results suggest that the receptor was diverted to proteasomal degradation. We also analysed the machinery responsible for lysosomal hydrolase transport to the lysosome and found increased stability of CIMPR, a major receptor implicated in the transport of hydrolases. The subcellular distribution of the CI-MPR was also altered in CLN3 cells, since it accumulated within the Trans-Golgi network (TGN) and did not progress into the lysosomes. In addition, we found a reduced turnover of retromer subunits, a complex that retrieves the CI-MPR from endosomes to the TGN. Finally and as a possible consequence of these alterations in lysosomal enzyme transport, cathepsin L and D maturation were found suppressed in CLN3 cells.

Altogether, these results point to increased lisosomal pH as a pivotal event causing various alterations in intracellular traffic associated to the development of JNCL disease.