Molecular and epidemiological trends of human bocavirus and adenovirus in children with acute gastroenteritis in Bangladesh during 2015-2019.
- 作者列表："Sharif N","Parvez AK","Haque A","Talukder AA","Ushijima H","Dey SK
Virus associated diarrhea remains one of the leading causes of children morbidity and mortality in Bangladesh. Human bocavirus (HBoV) has been reported as a potential pathogen of children diarrhea worldwide. However, due to its frequent association with other gastroenteric pathogens its role as diarrhea causative agent remains to be defined. This study focuses to detect the incidence of HBoV and adenovirus (AdV) and to determine molecular and epidemiological characteristics of HBoV and AdV. Between January 2015 to January 2019, 290 fecal specimens were collected from diarrheal children in Bangladesh. All fecal specimens were tested for HBoV and AdV by conventional polymerase chain reaction and sequencing methods. HBoV was detected in 7.24% (21 of 290) of the stool samples, as a sole virus in 71.42% (15 of 21) of the positive samples. Adenovirus was detected in 4.82% (14 of 290) of the samples. The most common clinical symptoms of HBoV infected patients were diarrhea (100%) and vomiting (57%). All of the isolates of HBoV were from HBoV1 and AdV were from AdV41, AdV5, AdV7 & AdV8. To the best of our knowledge this is the first epidemiological and molecular analysis report of HBoV from clinical specimens in Bangladesh. In future more studies are needed to clarify the role of HBoV as diarrheal pathogens. This article is protected by copyright. All rights reserved.
病毒相关性腹泻仍然是孟加拉国儿童发病和死亡的主要原因之一。人类博卡病毒 (HBoV) 已被报道为全球儿童腹泻的潜在病原体。然而，由于其经常与其他胃肠道病原体相关，其作为腹泻病原体的作用仍有待确定。本研究旨在检测 HBoV 和腺病毒 (AdV) 的发病率，并确定 HBoV 和 AdV 的分子和流行病学特征。在 2015年1月至 2019年1月期间，收集了 290 份来自孟加拉国腹泻儿童的粪便标本。所有粪便标本均采用常规聚合酶链反应和测序方法检测 HBoV 和 AdV。7.24% (290) 的粪便样本检出 HBoV，71.42% (21) 的阳性样本检出 HBoV 为单一病毒。4.82% (290 份中的 14 份) 的样本检测到腺病毒。HBoV 感染患者最常见的临床症状为腹泻 (100%) 和呕吐 (57%)。HBoV 的分离株均来自 HBoV1，AdV 分别来自 AdV41 、 AdV5 、 AdV7 和 adv8。据我们所知，这是孟加拉国第一份来自临床标本的 HBoV 流行病学和分子分析报告。未来还需要更多的研究来阐明 HBoV 作为腹泻病原体的作用。本文受版权保护。保留所有权利。
METHODS:Shigella species cause diarrheal disease globally. Shigellosis is typically characterized by bloody stools and colitis with mucosal damage and is the leading bacterial cause of diarrheal death worldwide. After the pathogen is orally ingested, it invades and replicates within the colonic epithelium through mechanisms that rely on its type III secretion system (T3SS). Currently, oral infection-based small animal models to study the pathogenesis of shigellosis are lacking. Here, we found that orogastric inoculation of infant rabbits with Shigella flexneri resulted in diarrhea and colonic pathology resembling that found in human shigellosis. Fasting animals prior to S. flexneri inoculation increased the frequency of disease. The pathogen colonized the colon, where both luminal and intraepithelial foci were observed. The intraepithelial foci likely arise through S. flexneri spreading from cell to cell. Robust S. flexneri intestinal colonization, invasion of the colonic epithelium, and epithelial sloughing all required the T3SS as well as IcsA, a factor required for bacterial spreading and adhesion in vitro Expression of the proinflammatory chemokine interleukin 8 (IL-8), detected with in situ mRNA labeling, was higher in animals infected with wild-type S. flexneri versus mutant strains deficient in icsA or T3SS, suggesting that epithelial invasion promotes expression of this chemokine. Collectively, our findings suggest that oral infection of infant rabbits offers a useful experimental model for studies of the pathogenesis of shigellosis and for testing of new therapeutics.IMPORTANCEShigella species are the leading bacterial cause of diarrheal death globally. The pathogen causes bacillary dysentery, a bloody diarrheal disease characterized by damage to the colonic mucosa and is usually spread through the fecal-oral route. Small animal models of shigellosis that rely on the oral route of infection are lacking. Here, we found that orogastric inoculation of infant rabbits with S. flexneri led to a diarrheal disease and colonic pathology reminiscent of human shigellosis. Diarrhea, intestinal colonization, and pathology in this model were dependent on the S. flexneri type III secretion system and IcsA, canonical Shigella virulence factors. Thus, oral infection of infant rabbits offers a feasible model to study the pathogenesis of shigellosis and to develop and test new therapeutics.
METHODS:PURPOSE:To quantify the effects of absorbed radiation dose on healthy liver parenchyma following radioembolisation (RE) using [99mTc]TcMebrofenin to analyse both global and regional liver function. METHODS:Patients having RE to treat hepatic disease underwent a [99mTc]TcMebrofenin hepatobilliary scintigraphy (HBS) study at both baseline and 8 weeks following treatment. Changes in global liver uptake rate were compared with healthy liver absorbed dose measures derived from the post-treatment 90Y PET/CT, including average dose, minimum dose to 70% of the volume (D70) and volume receiving at least 50 Gy (V50). Changes in functional burden associated with treatment and spared liver volumes in patients receiving lobar RE were also assessed, as were changes experienced by regional volumes corresponding to various dose ranges. Standard liver function pathology tests (LFTs) (bilirubin, albumin, ALP, AST, ALT and GGT) were examined for changes between baseline and post-treatment. RESULTS:Thirty-five patients were included in the study, of which, 9 had lobar treatment. A significant linear correlation was found between both baseline global liver uptake rate (negative) and D70 with change in global liver uptake rate. Patients undergoing lobar treatments demonstrated a shift in functional burden, and a significant difference was seen between the mean dose corresponding to liver volumes that increased their functional burden (9 Gy) and those that decreased their functional burden (35 Gy). No baseline LFTs predicted a decrease in global liver function; however, D70 demonstrated a linear correlation with changes in bilirubin and GGT. CONCLUSIONS:Given the significant negative relationship between baseline and change in global liver uptake rate, baseline HBS studies should not be used alone to disqualify patients considered for RE. In terms of treatment planning and evaluation, D70 may be the most appropriate metric of dose, with values greater than 15 Gy indicative of a likely drop in global liver function. The evidence of increasing functional burden in spared liver volumes suggests that patients at risk of complications could benefit from a lobar approach to treatment.
METHODS:NLRP3 inflammasome may serve as a potential target for the development of novel therapeutics for inflammatory bowel diseases. In this study, we found that Libertellenone M (Lib M), a secondary metabolite from the endophytic fungus Phomopsis sp. S12, has anti-inflammatory potential both in vitro and in vivo. Lib M selectively inhibited the expression of proinflammatory cytokine IL-1β and IL-18 in LPS-activated macrophages. The cleavage of pro-caspase 1 was remarkably reduced by Lib M in macrophages stimulated with three NLRP3 inflammasome activators. Administering Lib M attenuated dextran sulfate sodium-induced experimental acute colitis in mice and significantly reduced the production of these cytokines and cleaved caspase 1 in colon tissues. Apart from inhibition of NLRP3 inflammasome assembly, Lib M also suppressed NF-κB nuclear translocation in macrophages. Taken together, these findings suggest that Lib M-mediated inhibition of NLRP3 inflammasome activation could protect against colitis-like inflammatory diseases, and that this compound derived from a plant-associated fungus might inspire the exploration of novel immunosuppressive agents.