Systemic sclerosis (SSc) is an autoimmune disorder characterized by fibrosis of the skin and internal organs. Despite several studies on SSc treatments, effective treatments for SSc are still lacking. Since evidence suggests an association between intestinal microbiota and SSc, we focused on butyrate, which has beneficial effects in autoimmune diseases as a bacterial metabolite. Here, we investigated the therapeutic potential of sodium butyrate (SB) using a bleomycin-induced fibrosis mouse model of SSc and human dermal fibroblasts (HDFs). SB attenuated bleomycin-induced dermal and lung fibrosis in mice. SB influenced fecal microbiota composition (phyla Actinobacteria and Bacteroidetes, genera Bifidobacterium and Ruminococcus_g2). SB controlled macrophage differentiation in mesenteric lymph nodes, spleen, and bronchoalveolar lavage cells of mice with bleomycin-induced skin fibrosis. Profibrotic and proinflammatory gene expression was suppressed by SB administration in skin. Furthermore, SB inhibited transforming growth factor β1-responsive proinflammatory expression with increased acetylation of histone 3 in HDFs. Subcutaneous SB application had antifibrogenic effects on the skin. Butyrate ameliorated skin and lung fibrosis by improving anti-inflammatory activity in a mouse model of SSc. Butyrate may exhibit indirect and direct anti-fibrogenic action on fibroblasts by regulating macrophage differentiation and inhibition of histone deacetylase 3. These findings suggest butyrate as an SSc treatment.

Background: Escherichia coli is an important cause of diarrhea in calves and its diarrheagenic properties are related to presence of certain virulence genes. In this study, the prevalence of virulence genes F5, F17, F41, sta, stx1, stx2, eae, and saa in E. coli isolated from pre-weaned calves presenting with (n= 329) or without diarrhea (n= 360) was explored using multiplex polymerase chain reaction. We also evaluated the association between detection of E. coli and the presence of diarrhea. Results: Escherichia coli was detected in 56.3% (388/689) of the fecal samples and showed the highest prevalence (66.5%) in 21–40-day-old calves and the lowest (46.3%) among those that were 1–20 days old. The prevalence of the enterotoxigenic E. coli (ETEC) and Shiga toxin-producing E. coli (STEC) pathotypes was detected in 73.9% and 15.9%, respectively. The results showed no association between diarrhea and the presence of E. coli in general, ETEC or STEC. The F17 gene was the most frequently detected virulence factor in E. coli of calves of all ages regardless of diarrhea. Interestingly, the results show that the calves aged 41–60 days with F17-positive E. coli are at a higher risk for production of Shiga toxin (Stx1; 95% confidence intervals: 1.86–31.95; P = 0.005) compared to calves aged 1–20 days; no association between this finding and diarrhea was observed among the calves of this age group. Moreover, the virulence genes associated with the ETEC and STEC strains were not significantly associated with pathogenicity in this study cohort. Conclusions: These results suggest that while the incidence of E. coli is age-related, there was no relationship linking E. coli virulence genes to calf age and diarrhea. Furthermore, the present study demonstrated that detection of E. coli strains either with or without virulence factors was not associated with diarrhea in pre-weaned calves.

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disease with unknown etiology characterized by multi-organ fibrosis. Despite substantial investigation on SSc-related cellular and molecular mechanisms, effective therapies are still lacking. The skin, lungs, and gut are the most affected organs in SSc, which act as physical barriers and constantly communicate with colonized microbiota. Recent reports have documented a unique microbiome signature, which may be the pathogenic trigger or driver of SSc. Since gut microbiota influences the efficacy and toxicity of oral drugs, evaluating drug–microbiota interactions has become an area of interest in disease treatment. The existing evidence highlights the potential of the microbial challenge as a novel therapeutic option in SSc. In this review, we have summarized the current knowledge about molecular mechanisms of SSc and highlighted the underlying role of the microbiome in SSc pathogenesis. We have also discussed the latest therapeutic interventions using microbiomes in SSc, including drug–microbiota interactions and animal disease models. This review aims to elucidate the pathophysiological connection and therapeutic potential of the microbiome in SSc. Insights into the microbiome will significantly improve our understanding of etiopathogenesis and developing therapeutics for SSc.

Serious disease outbreaks in cattle caused by Theileria orientalis have emerged in the Asia–Pacific region. Genetic variables of the major piroplasm surface protein (MPSP) expressed on the surface of the piroplasm inside T. orientalis-infected erythrocytes are considered to be associated with variation in the pathogenicity of T. orientalis. Our study describes the clinically relevant MPSP types associated with anemia in Theileria-infected cattle. These results revealed that MPSP expression plays an important role in hematological alterations in Theileria-infected cattle, and that MPSP type 1 is strongly associated with bovine anemia, which can be a potential target for the prevention of bovine theileriosis.

Peroxiredoxin V (Prdx V) plays a major role in preventing oxidative damage as an effective antioxidant protein within a variety of cells through peroxidase activity. However, the function of Prdx V is not limited to peroxidase enzymatic activity per se. It appears to have unique function in regulating cellular response to external stimuli by directing interaction with signaling protein. In this study, we identified Prdx V interacting partners in mouse kidney under hypoxic stress using immunoprecipitation and shotgun proteomic analysis (LC-MS/MS). Immunoprecipitation coupled with nano-UPLC-MS^E shotgun proteomics was employed to identify putative interacting partners of Prdx V in mouse kidney in the setting of hypoxia. A total of 17 proteins were identified as potential interacting partners of Prdx V by a comparative interactomics analysis in kidney under normoxia versus hypoxia. Dihydrolipoamide branched chain transacylase E2 (DBT) appeared to be a prominent candidate protein displaying enhanced interaction with Prdx V under hypoxic stress. Moreover, hypoxic kidney exhibited altered DBT enzymatic activity compared to normoxia. An enhanced colocalization of these two proteins under hypoxic stress was successfully observed in vitro. Furthermore, peroxidatic cysteine residue (Cys48) of Prdx V is likely to be responsible for interacting with DBT. We identified several proteins interacting with Prdx V under hypoxic condition known to induce renal oxidative stress. In hypoxic condition, we observed an enhanced interaction of Prdx V and DBT protein as well as increased DBT enzymatic activity. The results from this study will contribute to enhance our understanding of Prdx V’s role in hypoxic stress and may suggest new directions for future research.

Raising cattle on pastures is known to be beneficial for animal welfare and cost reduction. However, grazing is associated with the risk of contracting tick-borne diseases, such as theileriosis. Here, the efficacy of ivermectin against these diseases and associated clinical symptoms were evaluated. A total of 68 cattle from a grazing cattle farm were selected and divided into two groups: the control group (17 cattle) with no preventive treatment and the ivermectin-treated group (51 cattle) in which cattle were treated with pour-on ivermectin prior to grazing. The infection rates of Theileria orientalis and the red blood cell (RBC) profile (e.g., RBC count, hematocrit value, and hemoglobin concentration) were compared in the spring (before grazing) and summer (during grazing) between the two groups. Based on PCR amplification of the major piroplasm surface protein (MPSP) gene, 12 cattle were positive for T. orientalis infection. Phylogenetic analysis revealed that the isolates identified in this study consisted of three MPSP types (1, 2, and 7). The T. orientalis infection rate in the control group during grazing was 3-fold higher than that in the ivermectin-treated group. Moreover, differences in RBC parameters during grazing were greater in the control group than in the ivermectin-treated group. In particular, the hematocrit value was significantly reduced in the control group. The results of this study demonstrated that ivermectin had protective effects against T. orientalis infection and RBC hemolysis in grazing cattle.