Klausenfletcher0080

Major conclusions Evidence supports that osteocalcin has a protective role in cardiometabolic health, and an increase of lipocalin 2 contributes to the development of cardiometabolic diseases partly via pro-inflammatory effects. The roles of sclerostin appear to be complicated It exerts pro-adiposity and pro-insulin resistance effects in type 2 diabetes and has an anti-calcification effect during cardiovascular disease. A better understanding of the actions of these bone-derived hormones in the pathophysiology of cardiometabolic diseases will provide crucial insights to help further research develop new therapeutic strategies to treat these diseases.Candida auris is an emerging fungal species able to develop multidrug resistance and outbreaks of invasive infections worldwide with high mortality rates. To increase the treatment options for C. auris infection, we assessed the efficacy of miltefosine (MFS), an anti-Leishmania agent that has demonstrated a broad-spectrum antifungal action in vitro. The aims of this work were (i) to evaluate the in vitro antifungal activity of MFS against C. auris clinical isolates in the planktonic and biofilm lifestyles; and (ii) to compare the activity of MFS in its free form and encapsulated in alginate nanoparticles (MFS-AN) in Galleria mellonella larvae infected by C. auris. MFS exhibited in vitro inhibitory effect at MICs ranging from 1 to 4 µg/mL and fungicidal activity against planktonic cells of C. auris clinical isolates. MFS antibiofilm activity was observed during biofilm formation (0.25 to 4 µg/mL) and on pre-formed biofilms (16 to 32 µg/mL). Moreover, the dispersed cells from C. auris biofilms had a similar susceptibility to those obtained for planktonic cells. Treatment with free MFS or MFS-AN resulted in significant improvements in the survival and morbidity rates of G. mellonella larvae infected by C. auris. In addition, reduction of fungal burden (0.5-1 log CFU/g) and granuloma formation were observed when compared with the untreated group. Our findings suggest that both the free MFS and MFS-AN have potential for the treatment of fungal infections caused by the emerging C. auris.Clonal complex 59 (CC59) is the dominant community-associated methicillin-resistant Staphylococcus aureus (MRSA) strain in Taiwan and includes the Asian-Pacific clone with Panton-Valentine leukocidin (PVL)-negative/staphylococcal cassette chromosome mec (SCCmec) IVg and the Taiwan clone characterised as PVL-positive/SCCmec V (5C2&5). Nevertheless, data on the evolutionary history of the two dominant CC59 MRSA clones in Taiwan are scarce. In this study, a total of 258 CC59 S. aureus strains from Taiwan were classified by multiple-locus variable-number tandem repeat analysis (MLVA), which revealed two major clusters (MT1 and MT2) with distinct mobile genetic elements (MGEs). However, sequencing and PCR mapping of the β-lactamase-producing plasmid revealed no difference among all CC59 S. aureus strains. Bayesian evolutionary analysis of 18 of the CC59 S. aureus strains based on core genome alignment revealed two clades (i) Clade A, which shared the samples with MT1, had the features of mainly harbouring gentamicin-resistant MES6272-2 or MES4578, φSA3 translocation in νSaβ and SCCmec IVg; and (ii) Clade B, which shared the samples with MT2, had the features of mainly harbouring streptomycin-resistant MESPM1, PVL phage and SCCmec V (5C2&5). Based on the time-calibrated phylogenetic tree, the estimated time of divergence of the two clades was in the 1980s. These results suggest that the CC59 S. aureus progenitor acquired a β-lactamase-producing plasmid and then developed the varied genetic backgrounds, which were associated with the acquisition and maintenance of distinct MGEs, leading to differences in antimicrobial susceptibility profiles and molecular virulence determinants.Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) have disseminated worldwide and emerged as major threats to public health. The multidrug-resistant (MDR)-phenotype of KPC-KP are commonly associated with the presence of high molecular weight blaKPC plasmids. Restriction-modification (R-M) systems provide bacteria with innate defense against plasmids or other infectious gene elements. Because of blaKPC plasmids are favored by such MDR K. pneumoniae, it was of interest to examine the co-distribution of R-M and acquired blaKPC plasmids in KPC-KP. We collected 459 clinical K. AY-22989 pneumoniae isolates in China and 217 global whole-genome sequences in GenBank to determine the prevalence of type I R-M systems. We found the type I R-M system was significantly scarce in the KPC-positive group and high risk Klebsiella pneumoniae clonal group 258 (CG258). The polymorphisms of type I R-M we observed in K. pneumoniae reveled the relative ubiquity of their recognition sequences in DNA, which means the type I R-M systems were capable to attack most invading DNA elements, such as blaKPC genes. Overall, our work suggested the type I R-M systems may impact the acquisition of blaKPC genes in K. pneumoniae.Purpose Conjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection. Methods We analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2. Results Across all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, Western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2. Conclusions Together, these results suggest that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.