This study was conducted to compare effects of 3 physical forms of feed including mash (diet 1), pellet (diet 2) and complete feed block (CFB; diet 3) on digestion, fermentation and performance of lambs. Twenty-one lambs with an initial average body weight of 26 ± 2.5 kg and 6 ± 1.5 months of age were assigned through a completely randomized design to 3 treatments and 7 replicates. The experimental treatments had the same formulation. The results of present experiment showed that CFB significantly increased feed intake and nutrient digestibility (P < 0.05). There was no significant difference among the diets for rumen fluid pH, blood glucose, concentration of volatile fatty acids (P > 0.05), except acetic acid (P < 0.05). The rumen ammonia nitrogen (NH3—N), mixed rumen protozoa population (RPP), Entodiniums spp., Epidiniums spp., blood urea nitrogen (BUN) concentration, rumination time adjusted for dry matter (DM), neutral detergent fiber (NDF), acid detergent fiber (ADF) intake, and total body weight gain of lambs in CFB diet were the highest among all diets (P < 0.05). Feed conversion ratio at days 31 to 45 and whole experimental period were better in CFB than in other diets (P < 0.05). Overall, according to the findings of the present study, among 3 physical forms of the diets, CFB had the best efficiency due to improvement of nutrient digestibility, rumen fermentation and performance of lambs. Therefore, the CFB diet offers the best result in lambs compared with mash and pellet diets.

The most prominent feature of systemic sclerosis (SSc) and other diseases associated with fibrosis is the prolonged activation of fibroblasts not eliminated by apoptosis, hence characterized by accumulation of more extra cellular matrix (ECM). We tend to verify if microRNA-29a (miR-29a) as an anti-fibrotic factor could induce apoptosis in SSc fibroblasts. We did not detect apoptosis in SSc fibroblasts. We found that Bcl-2 expression was upregulated in SSc fibroblasts and the ratio of Bax:Bcl-2 in these cells was significantly lower (p = 0.02) compared to normal fibroblasts. Transfection of both SSc and transforming growth factor-β (TGF-β) stimulated fibroblasts by miR-29a mimic, significantly decreased the expression of two anti-apoptotic members of the Bcl-2 family, Bcl-2 (p = 0.0005, p = 0.01) and Bcl-XL (p = 0.0001, p = 0.006), resulted in enhanced Bax:Bcl-2 ratio and induced a high rate of apoptosis. Recently, miR-29 has been introduced as an anti-fibrotic factor with potential therapeutic effect on SSc. Until now, it has not been proposed whether there is a relationship between miR-29a and apoptosis in SSc. According to our results, it seems that miR-29a is a potent inducer of apoptosis in SSc fibroblasts and an attenuator of ECM production in these cells. MiR-29a disrupted the expression profiling of Bcl-2 family proteins (Bax, Bcl-2 and Bcl-XL) which is the central point of dynamic life-death rheostat in many apoptotic pathways. Furthermore, dermal fibroblasts from patients with SSc showed elevation in TNF-α mRNA levels, while restoration of miR-29a decreases TNF-α production in these cells. Although further molecular studies are necessary to investigate the underlying apoptotic pathways, the present findings suggest that anti-fibrotic and pro-apoptotic properties of miR-29a could provide novel benefits toward the development of fibroblast-specific anti-fibrotic therapies.

Background: Systemic sclerosis (SSc), a multi-organ disorder, is characterized by vascular abnormalities, dysregulation of the immune system, and fibrosis. The mechanisms underlying tissue pathology in SSc have not been entirely understood. This study intended to investigate the common and tissue-specific pathways involved in different tissues of SSc patients. Methods: An integrative gene expression analysis of ten independent microarray datasets of three tissues was conducted to identify differentially expressed genes (DEGs). DEGs were mapped to the search tool for retrieval of interacting genes (STRING) to acquire protein-protein interaction (PPI) networks. Then, functional clusters in PPI networks were determined. Enrichr, a gene list enrichment analysis tool, was utilized for the functional enrichment of clusters. Results: A total of 12, 2, and 4 functional clusters from 619, 52, and 119 DEGs were determined in the lung, peripheral blood mononuclear cell (PBMC), and skin tissues, respectively. Analysis revealed that the tumor necrosis factor (TNF) signaling pathway was enriched significantly in the three investigated tissues as a common pathway. In addition, clusters associated with inflammation and immunity were common in the three investigated tissues. However, clusters related to the fibrosis process were common in lung and skin tissues. Conclusions: Analysis indicated that there were common pathological clusters that contributed to the pathogenesis of SSc in different tissues. Moreover, it seems that the common pathways in distinct tissues stem from a diverse set of genes.

Although further studies are necessary to determine the underlying apoptotic pathway, we propose that inhibition of miR-21 in dermal fibroblasts from lesional skin may be useful in harnessing progressive fibrosis in SSc.