Studying a propionic acidaemia mouse model reveals epigenetic mechanisms in the heart

We show how a build-up of propionyl-CoA in a mouse model of propionic acidaemia produces histone modifications in the heart. The transcriptional responses included genes implicated in contractile dysfunction. Notably, female mice are more severely affected, owing to a protective effect of β-alanine in males, a therapeutically important finding

Distribution and antimicrobial resistance profiles of bacterial species in stray cats, hospital-admitted cats, and veterinary staff in South Korea

Antimicrobial resistance is becoming increasingly important in both human and veterinary medicine. According to the One Health concept, an important step is to monitor the resistance patterns of pathogenic bacteria. In this study, the antimicrobial susceptibility patterns and trends of bacteria isolated from stray cats, hospital-admitted cats, and veterinary staff in South Korea between 2017 and 2018 were investigated. The minimum inhibitory concentrations of different antibiotics for Staphylococcus spp., Enterobacteriaceae, and Enterococcus spp. were determined to establish representatives of different antibiotic classes relevant for treatment or surveillance. For Coagulase-positive and Coagulase-negative Staphylococci, resistance to fluoroquinolones was below 13%, but resistance to ampicillin and penicillin was high (20–88%). A total of 9.5, 12.1, and 40.3% of staphylococcal isolates from stray cats, hospital-admitted cats, and veterinary staff, respectively, were confirmed to be mecA positive. For Enterobacteriaceae, resistance to carbapenems, fluoroquinolones, and 3rd generation cephalosporins was low (0–11.1%). The Enterococcus spp. isolates showed no resistance to vancomycin. The antimicrobial resistance rates of the Staphylococcus spp. and Enterobacteriaceae isolates from stray cats were usually lower than those of isolates from hospital-admitted cats and veterinary staff, but the Enterococcus spp. isolates revealed the opposite. Thus, the antimicrobial resistance varied across bacterial species according to the source from which they were isolated. Resistance to critically important compounds were low. However, the presence of antimicrobial resistance in cat isolates is of both public health and animal health concern.This work was supported by a grant from the Animal and Plant Quarantine Agency, Ministry of Agriculture and Forestry (Z-1543081-2017-18-03) and the Cooperative Research Program of Center for Companion Animal Research Jung et al. BMC Veterinary Research (2020) 16:109 Page 12 of 14 (Project No. PJ013985022019) of Rural Development Administration, South Korea. The funding bodies played no role in the design of the study, the collection, analysis, and interpretation of data and in writing the manuscript

One-pot Enzymatic Synthesis of Deoxy-thymidine-diphosphate (TDP)-2-deoxy-∝-d-glucose Using Phosphomannomutase

Production of deoxy-thymidine-diphosphate (TDP)-sugars as substrates of glycosyltransferases, has been one of main hurdles for combinatorial antibiotic biosynthesis, which combines sugar moiety with aglycon of various antibiotics. Here, we report the one-pot enzymatic synthesis of TDP-2-deoxy-glucose employing high efficient TMP kinase (TMK; E.C. 2.7.2.12), acetate kinase (ACK; E.C. 2.7.1.21), and TDP-glucose synthase (TGS; E.C. 2.7.7.24) with phosphomannomutase (PMM; E.C. 5.4.2.8). In this study, replacing phosphoglucomutase (PGM; E.C. 5.4.2) by PMM from Escherichia coli gave four times higher specific activity on 2-deoxy-6-phosphate glucose, suggesting that the activity on 2-deoxy-glucose-6-phosphate was mainly affected by PMM activity, not PGM activity. Using an in vitro system starting from TMP and 2-deoxy-glucose-6-phosphate glucose, TDP-2-deoxy-glucose (63% yield) was successfully synthesized. Considering low productivity of NDP-sugars from cheap starting materials, this paper showed how production of NDP-sugars could be enhanced by controlling mutase activity

Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug's reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity

Percutaneous Endoscopic Lumbar Foraminoplasty for Resection of Synovial Cyst

Synovial cyst is an extradural mass that compresses nerve root or thecal sac. Surgical excision with partial hemilaminectomy and medial facetectomy is commonly used for synovial cyst. Remarkable advancements in endoscopic spinal surgery have led to successful outcomes comparable to conventional open surgery. Here we introduce percutaneous endoscopic lumbar foraminoplasty for resecting synovial cyst as a minimal invasive technique. A 59-year-old woman presented with radicular pain at left L5 dermatome. Magnetic resonance images demonstrated a synovial cyst at left L4-5 facet joint and degenerative spondylolisthesis on L4-5. Under endoscopy, synovial cyst was removed by piecemeal method after transforaminal endoscopic foraminoplasty that removed part of superior facet. Her symptoms were relieved and the patient was discharged the next day. Therefore, percutaneous endoscopic lumbar foraminoplasty can be used as a minimally invasive surgical option for synovial cyst. It may provide less traumatization and affect less postoperative instability