Combating increased antifungal drug resistance in Cryptococcus, what should we do in the future?

Few therapeutic drugs and increased drug resistance have aggravated the current treatment difficulties of Cryptococcus in recent years. To better understand the antifungal drug resistance mechanism and treatment strategy of cryptococcosis. In this review, by combining the fundamental features of Cryptococcus reproduction leading to changes in its genome, we review recent research into the mechanism of four current anti-cryptococcal agents, coupled with new therapeutic strategies and the application of advanced technologies WGS and CRISPR-Cas9 in this field, hoping to provide a broad idea for the future clinical therapy of cryptococcosis

Molecular epidemiology and microbiological characteristics of Cryptococcus gattii VGII isolates from China.

Cryptococcus gattii (C. gattii) is a fungal pathogen that once caused an outbreak of cryptococcosis on Vancouver Island, and had spread worldwide, while few data were available in China. In this study, seven clinical isolates of C. gattii VGII were collected from 19 hospitals, Multi-locus Sequence Typing (MLST) analysis and whole-genome sequencing (WGS) was performed, combined with published data for phylogenetic analysis. In addition, in vitro antifungal susceptibility testing, phenotypic analysis, and in vivo virulence studies were performed, subsequently, histopathological analysis of lung tissue was performed. C.gattii VGII infected patients were mainly immunocompetent male, and most of them had symptoms of central nervous system (CNS) involvement. MLST results showed that isolates from China exhibited high genetic diversity, and sequence type (ST) 7 was the major ST among the isolates. Some clinical isolates showed a close phylogenetic relationship with strains from Australia and South America. All clinical isolates did not show resistance to antifungal drugs. In addition, there was no correlation between virulence factors (temperature, melanin production, and capsule size) and virulence while in vivo experiments showed significant differences in virulence among strains. Lung fungal burden and damage to lung tissue correlated with virulence, and degree of damage to lung tissue in mice may highlight differences in virulence. Our work seeks to provide useful data for molecular epidemiology, antifungal susceptibility, and virulence differences of C. gattii VGII in China

Calcium supplementation increases circulating cholesterol by reducing its catabolism via GPER and TRPC1-dependent pathway in estrogen deficient women

Background: Limited studies have addressed the effects of calcium supplementation (CaS) on serum total cholesterol (TC) in postmenopausal women and the results are inconclusive. Moreover, the potential mechanisms through which CaS regulates cholesterol metabolism in the absence of estrogen are still sealed for the limitation of human being study. Methods: Cross-sectional survey, animal and in vitro experiments were conducted to investigate the effect of CaS on endogenous cholesterol metabolism in estrogen de\ufb01ciency and identify its potential mechanisms. Ovariectomized rats were used to mimic estrogen de\ufb01ciency. In vitro, HepG2 cell line was exposed to estradiol and/or calcium treatment. Results: We demonstrated that CaS signi\ufb01cantly increased serum TC and the risk of hypercholesterolemia and myocardial infarction in postmenopausal women. Increased serum TC in estrogen de\ufb01ciency was caused mainly by decreased cholesterol catabolism rather than increased synthesis. This was mediated by reduced 7\u3b1-hydroxylase resulting from increased liver intracellular Ca\ub2\u207a concentrations, reduced intracellular basal cAMP and subsequent up-regulation of SREBP-1c and SHP expression. Estrogen had a protective role in preventing CaS-induced TC increase by activating the G-protein coupled estrogen receptor, which mediated the estrogen effect through the transient receptor potential canonical 1 cation channel. Conclusions: CaS increases endogenous serum TC via decreasing hepatic cholesterol catabolism in estrogen de\ufb01ciency. G-protein coupled estrogen receptor is shown to be a key target in mediating CaS-induced TC increase. CaS should be monitored for the prevention of serum TC increase during menopause.Peer reviewed: YesNRC publication: Ye

Human Chrysomya bezziana myiasis: A systematic review.

BACKGROUND:Myiasis due to Old World screw-worm fly, Chrysomya bezziana, is an important obligate zoonotic disease in the OIE-list of diseases and is found throughout much of Africa, the Indian subcontinent, southeast and east Asia. C. bezziana myiasis causes not only morbidity and death to animals and humans, but also economic losses in the livestock industries. Because of the aggressive and destructive nature of this disease in hosts, we initiated this study to provide a comprehensive understanding of human myiasis caused by C. bezziana. METHODS:We searched the databases in English (PubMed, Embase and African Index Medicus) and Chinese (CNKI, Wanfang, and Duxiu), and international government online reports to 6th February, 2019, to identify studies concerning C. bezziana. Another ten human cases in China and Papua New Guinea that our team had recorded were also included. RESULTS:We retrieved 1,048 reports from which 202 studies were ultimately eligible for inclusion in the present descriptive analyses. Since the first human case due to C. bezziana was reported in 1909, we have summarized 291 cases and found that these cases often occurred in patients with poor hygiene, low socio-economic conditions, old age, and underlying diseases including infections, age-related diseases, and noninfectious chronic diseases. But C. bezziana myiasis appears largely neglected as a serious medical or veterinary condition, with human and animal cases only reported in 16 and 24 countries respectively, despite this fly species being recorded in 44 countries worldwide. CONCLUSION:Our findings indicate that cryptic myiasis cases due to the obligate parasite, C. bezziana, are under-recognized. Through this study on C. bezziana etiology, clinical features, diagnosis, treatment, epidemiology, prevention and control, we call for more vigilance and awareness of the disease from governments, health authorities, clinicians, veterinary workers, nursing homes, and also the general public