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1.
Bioengineered ; 12(1): 310-324, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33446013

RESUMO

In clinical practice, we found that microRNA (miR)-146a-5p is significantly up-regulated in peripheral blood mononuclear cells (PBMCs) of primary sjögren's syndrome (pSS) patients. In vitro experiments confirmed that miR-146a-5p promotes T helper 17 (Th17) cell differentiation, but the specific mechanism is still unknown. To solve this problem, 20 pSS patients and 20 healthy subjects were enrolled in this study and PBMCs were isolated from their blood. The expression of the membrane IL-23 R (mIL-23 R) in PBMCs was determined. CD3+ T cells were also isolated and used to further analyze the relationship between the ectodomain shedding of mIL-23 R and a disintegrin and metalloprotease 17 (ADAM17). Finally, miR-146a-5p inhibitor and mimics were transfected into PBMCs to evaluate the relationship between ADAM17 and mIL-23 R, and explore the role of mIL-23 R and ADAM17 in Th17 cell differentiation. Our results revealed a significantly increased expression of miR-146a-5p in PBMCs from pSS patients and significantly increased percentage of Th17 cells compared to PBMCs from healthy controls. Under polarization culture conditions, pSS patient-derived PBMCs can more easily differentiate into Th17 cells, which was, to a great extent, attributable to the increased expression of mIL-23 R. Moreover, ADAM17, an ectodomain sheddase of mIL-23 R, was targeted and negatively regulated by miR-146a-5p, which reduced the ectodomain shedding of mIL-23 R. Overall, our results suggested that miR-146a-5p could promote Th17 cell differentiation through targeting and negatively regulating ADAM17. Thus, these results might offer a new approach in the treatment of pSS.

2.
BMC Biol ; 19(1): 5, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33441133

RESUMO

BACKGROUND: Viruses are ubiquitous biological entities, estimated to be the largest reservoirs of unexplored genetic diversity on Earth. Full functional characterization and annotation of newly discovered viruses requires tools to enable taxonomic assignment, the range of hosts, and biological properties of the virus. Here we focus on prokaryotic viruses, which include phages and archaeal viruses, and for which identifying the viral host is an essential step in characterizing the virus, as the virus relies on the host for survival. Currently, the method for determining the viral host is either to culture the virus, which is low-throughput, time-consuming, and expensive, or to computationally predict the viral hosts, which needs improvements at both accuracy and usability. Here we develop a Gaussian model to predict hosts for prokaryotic viruses with better performances than previous computational methods. RESULTS: We present here Prokaryotic virus Host Predictor (PHP), a software tool using a Gaussian model, to predict hosts for prokaryotic viruses using the differences of k-mer frequencies between viral and host genomic sequences as features. PHP gave a host prediction accuracy of 34% (genus level) on the VirHostMatcher benchmark dataset and a host prediction accuracy of 35% (genus level) on a new dataset containing 671 viruses and 60,105 prokaryotic genomes. The prediction accuracy exceeded that of two alignment-free methods (VirHostMatcher and WIsH, 28-34%, genus level). PHP also outperformed these two alignment-free methods much (24-38% vs 18-20%, genus level) when predicting hosts for prokaryotic viruses which cannot be predicted by the BLAST-based or the CRISPR-spacer-based methods alone. Requiring a minimal score for making predictions (thresholding) and taking the consensus of the top 30 predictions further improved the host prediction accuracy of PHP. CONCLUSIONS: The Prokaryotic virus Host Predictor software tool provides an intuitive and user-friendly API for the Gaussian model described herein. This work will facilitate the rapid identification of hosts for newly identified prokaryotic viruses in metagenomic studies.

3.
Front Oncol ; 10: 560487, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262941

RESUMO

Evidence for research over the past decade shows that epigenetic regulation mechanisms run through the development and prognosis of tumors. Therefore, small molecular compounds targeting epigenetic regulation have become a research hotspot in the development of cancer therapeutic drugs. According to the obvious abnormality of histone acetylation when tumors occur, it suggests that histone acetylation modification plays an important role in the process of tumorigenesis. Currently, as a new potential anti-cancer therapeutic drugs, many active small molecules that target histone acetylation regulatory enzymes or proteins such as histone deacetylases (HDACs), histone acetyltransferase (HATs) and bromodomains (BRDs) have been developed to restore abnormal histone acetylation levels to normal. In this review, we will focus on summarizing the changes of histone acetylation levels during tumorigenesis, as well as the possible pharmacological mechanisms of small molecules that target histone acetylation in cancer treatment.

5.
Medicine (Baltimore) ; 99(48): e23409, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33235120

RESUMO

BACKGROUND: Talaromyces marneffei (T marneffei), known as a significant pathogen in patients with AIDS in Southeast Asia, is a dimorphic fungus, which can cause deadly systematic infection in immunocompromised hosts. What is more, the dimorphic phase transition has been reported as a conspicuous process linked with virulence. Interestingly, the yeast form was found in infected individuals, representing the pathogenic phase. However, few researches were found to study the mechanism of dimorphic transition. Thus, a diverse insight into the dimorphic switch mechanism, is urgently needed and we are the first one to research the mechanism of dimorphism. METHODS: Firstly, we investigated the microarray of T. marneffei in the Gene Expression Omnibus database (GEO) for differentially expressed genes (DEGs). Then Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8 was employed to analyze the underlying enrichment and pathway in biological process of DEGs. Meanwhile, protein-protein interaction (PPI) network was constructed using STRING database. On the strength of the theory that similar amino acid sequences share similar structures, which play a decisive role on the function of protein, three dimensional structures of hub-genes were predicted to further investigate the likely function of hub-genes. RESULTS: GSE51109 was elected as the eligible series for the purpose of our research, including GSM1238923 (GSM23), GSM1238924 (GSM24), and GSM1238925 (GSM25). PMAA_012920, PMAA_028730, PMAA_068140, PMAA_092900, PMAA_032350 were the most remarkable genes in all of the three PPI networks, thus, were viewed as hub-genes. With regard to the three-dimensional construction, except that there was no significant prediction structure of PMAA_092900 with the criterion seq identify > 30%, GMQE: 0-1, QMEAN4: -4-0, the parallel templates for four structures were Crystal structure of Saccharomyces cerevesiae mitochondrial NADP(+)-dependent isocitrate dehydrogenase in complex with isocitrate, Organellar two-pore channels (TPCs), Yeast Isocitrate Dehydrogenase (Apo Form) and Crystal Structure Of ATP-Dependent Phosphoenolpyruvate Carboxykinase From Thermus thermophilus HB8 in order. CONCLUSION: The dimorphic transition of T. marneffei was viewed as a pathogenic factor and DEGs were observed. In-depth study of the function and pathway of DEGs revealed that PMAA_012920, PMAA_028730, PMAA_068140, PMAA_092900, PMAA_032350 were most likely acting as the hub-genes and were likely taking effect through regulating energy metabolism.


Assuntos
Regulação Fúngica da Expressão Gênica , Talaromyces/genética , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Biologia Computacional , Bases de Dados Genéticas , Redes Reguladoras de Genes , Humanos , Micoses/microbiologia , Conformação Proteica , Mapas de Interação de Proteínas , Talaromyces/patogenicidade
6.
Sci Total Environ ; : 143142, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33168253

RESUMO

Modifying the surface of an anode can improve electroactive bacteria (EAB) enrichment, thereby enhancing the performance of the associated microbial electrochemical systems (MESs). In this study, biosynthetic FeS nanoparticles were used to modify the anode in MESs. The experimental results demonstrated that the stable maximum voltage of the FeS composited biochar (FeS/BC)-modified anode reached 0.72 V, which is 20% higher than that of the control. The maximum power density with the FeS/BC anode was 793 mW/m2, which is 46.31% higher than that obtained with the control (542 mW/m2). According to cyclic voltammetry (CV) analysis, FeS/BC facilitates the direct electron transfer between bacteria and the electrode. The biomass protein concentration of the FeS/BC anode was 841.75 µg/cm2, which is almost 1.5 times higher than that of the carbon cloth anode (344.25 µg/cm2); hence, FeS/BC modification can promote biofilm formation. The composition of Geobacter species on the FeS/BC anode (75.16%) was much higher than that on the carbon cloth anode (4.81%). All the results demonstrated that the use of the biosynthetic FeS/BC anode is an environmentally friendly and efficient strategy for enhancing the electroactive biofilm formation and EAB enrichment in MESs.

7.
Infect Drug Resist ; 13: 3811-3816, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33122926

RESUMO

Purpose: Talaromyces marneffei is a highly invasive fungus, causing fatal mycosis in patients with or without HIV in Southeast and Eastern Asia. However, its presence in patients with systemic lupus erythematosus is rarely reported. Methods: We reported two SLE patients infected by T. marneffei and reviewed other patients reported in the English literature. All cases were pooled for analysis. Results: Eleven patients with SLE infected with T. marneffei infection were identified, including the two presented here. Three were male and eight were female; all were HIV negative. All the patients, except two where data were missing, had received immunosuppressants before T. marneffei infection. The main clinical features included fever, cough, lymph node enlargement, gastrointestinal symptoms, and rash. Five patients were misdiagnosed as having SLE exacerbation. T. marneffei was detected via culture or histopathologic analysis, with the fungus most commonly found in the blood. Seven of the 11 patients were successfully treated by timely antifungal therapy with concomitant SLE control, while four patients who did not receive antifungal therapy died. Conclusion: T. marneffei infection should be excluded when SLE patients, especially if on long-term immunosuppressants, present with fever, cough, lymph node enlargement, gastrointestinal symptoms, and rash. Controlling the lupus and timely antifungal treatment can improve the outcomes of SLE patients with T. marneffei infection.

8.
Sleep Med ; 76: 48-54, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33091726

RESUMO

OBJECTIVES: To evaluate sleep duration in a representative sample of preschoolers and examine the relationships between screen time and use of different electronic media devices with sleep duration and social jetlag. METHODS: 2903 preschoolers were included. Parent-completed questionnaire provided information on socioeconomic status, electronic media use of the children and sleep patterns of both parents and children. Preschoolers were divided according to whether they met the international screen time recommendations for their age. Comparisons between the two groups in various sleep measures and effects of different devices on sleep were evaluated. RESULTS: 40% of preschoolers in our cohort did not achieve the recommended sleep duration. Subjects who adhered to the screen time recommendations were from families of higher socioeconomic status, had longer sleep duration and better sleep habits. Each hour increase on portable electronic device use was associated with 11 (95%CI: -15 to -6) and 6 (95%CI: -10 to -2) minutes less of average daily sleep duration in boys and girls, respectively. Every additional hour of non-portable electronic devices use was associated with 3 min shift in social jetlag in boys. Presence of electronic devices in bedroom and their use at bedtime increased risk of social jetlag in boys with an OR of 1.40 (95%CI: 1.01 to 1.92) and 1.39 (95%CI: 1.00 to 1.95) respectively. CONCLUSION: A significant proportion of preschoolers does not obtain the recommended amount of sleep. Screen time in preschoolers affects not only sleep duration but also leads to circadian discrepancy.

9.
Sustain Cities Soc ; 63: 102466, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32904401

RESUMO

The novel human coronavirus (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19) pandemic worldwide. Control of COVID-19 pandemic is vital for public health and is the prerequisite to maintain social stability. However, the origin and transmission route of SARS-CoV-2 is unclear, bringing huge difficult to virus control. Monitoring viral variation and screening functional mutation sites are crucial for prevention and control of infectious diseases. In this study, we developed a user-friendly software, named BioAider, for quick sequence annotation and mutation analysis on large-scale genome-sequencing data. Herein, we detected 14 substitution hotspots within 3,240 SARS-CoV-2 genome sequences, including 3 groups of potentially linked substitution. NSP13-Y541C was crucial substitution which might affect the unwinding activity of the viral helicase. In particular, we discovered a SR-rich region of SARS-CoV-2 distinct from SARS-CoV, indicating more complex replication mechanism and unique N-M interaction of SARS-CoV-2. Interestingly, the quantity of SSRX repeat fragments in SARS-CoV-2 provided further evidence of its animal origin. Overall, we developed an efficient tool for rapid identification of viral genome mutations which could facilitate viral genomic studies. Using this tool, we have found critical clues for the transmission route of SARS-CoV-2 which would provide theoretical support for the epidemic control of pathogenic coronaviruses.

10.
Eur J Nutr ; 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32979077

RESUMO

PURPOSE: Docosahexaenoic acid (DHA) plays an essential role in brain, and its status is dependent on dietary intakes. School-aged children in rural China, who consume diets low in omega-3 polyunsaturated fatty acids, may benefit from DHA supplementation. Therefore, this trial was performed to examine the effect of 6-month DHA supplementation on executive functions (EFs) among healthy school-aged children in rural China. METHODS: A randomized, double-blind, placebo-controlled trial was conducted among 106 primary school children aged 7-12 years in rural China. Participants were randomized to receive either 300 mg/d DHA or placebo for 6 months. EFs including working memory and cognitive flexibility were evaluated at baseline, at 3 months and at 6 months, using Digit Span Backwards and Wisconsin card sorting test, respectively. Socio-demographic data were collected at baseline, and erythrocyte membrane fatty acids and serum neurotransmitters were measured at baseline and after 6-month intervention. RESULTS: Ninety-four children (88.7%) completed the study according to the protocol. Changes in erythrocyte membrane fatty acids indicated good compliance of the participants. There was no significant intervention effect on serum neurotransmitters. In two-factor ANCOVA, both groups showed a significant improvement in the Digit Span Backwards and the Wisconsin card sorting test from baseline to endpoint. However, no significant intervention effect was found on any EF scores. Linear regression analysis suggested no significant association between changes in erythrocyte DHA level with changes in any EF scores. CONCLUSIONS: Supplementation with 300 mg/d DHA for 6 months had no benefit on EFs including working memory and cognitive flexibility among healthy school-aged children. This trial was registered at clinicaltrials.gov as NCT02308930 on December 5, 2014.

12.
Biosens Bioelectron ; 168: 112569, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32905930

RESUMO

Wearable and implantable bio-integrated electronics have started to gain momentum because of their essential role in improving the quality of life for various patients and healthy individuals. However, their continuous operation is often limited by traditional battery technologies with a limited lifespan, creating a significant challenge for their development. Thus, it is highly desirable to harvest biomechanical energies from human motion for self-powered bio-integrated functional devices. Piezoelectric energy harvesters are ideal candidates to achieve this goal by converting biomechanical energy to electric energy. Because of their applications on soft and highly deformable tissues of the human body, these devices also need to be mechanically flexible and stretchable, thus posing a significant challenge. Effective methods to address the challenge include the exploration of new stretchable piezoelectric materials (e.g., hybrid composite material) and stretchable structures (e.g., buckled shapes, serpentine mesh layouts, kirigami designs, among others). This review presents an overview of the recent developments in new intrinsically stretchable piezoelectric materials and rigid inorganic piezoelectric materials with novel stretchable structures for flexible and stretchable piezoelectric sensors and energy harvesters. Following the discussion of theoretical modeling of the piezoelectric materials to convert mechanical deformations into electrical signals, the representative applications of stretchable piezoelectric materials and structures in wearable and implantable devices are briefly summarized. The present limitations and future research directions of flexible and stretchable piezoelectric devices are then discussed.

13.
Bioorg Med Chem Lett ; 30(21): 127504, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32827631

RESUMO

25-OH ginsenosides are potent and rare prodrugs in natural sources. However current strategies for such modification always end up in undesirable side products and unsatisfied yield that hinders them from further applications. Herein, ginsenoside Rg1 was thoroughly converted into 20(S/R)-Rh1 and 25-OH-20(S/R)-Rh1 by Cordyceps Sinensis in an optimum medium. The chemical correctness of either 25-OH-20(S/R)-Rh1 epimers was validated by LC-IT-TOF-MSn and 13C NMR spectrometry. The biocatalytic pathway was established as Rg1 â†’ 20(S/R)-Rh1 â†’ 25-OH-20(S/R)-Rh1. The molar bioconversion rate for total 25-OH-20(S/R)-Rh1 was calculated to be 82.5%, of which S-configuration accounted for 43.2% while R-configuration 39.3%. These two 25-OH derivatives are direct hydration products from 20(S/R)-Rh1 without other side metabolites, suggesting this is a highly regioselective process. In conclusion, this biocatalytic system could be harnessed to facilitate the preparation of diversified 25-OH ginsenosides with high yields of the target compound and simple chemical background in the reaction mixture.

14.
Transbound Emerg Dis ; 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32794346

RESUMO

Coronavirus (CoV) pandemics have become a huge threat to the public health worldwide in the recent decades. Typically, severe acute respiratory syndrome CoV (SARS-CoV) caused SARS pandemic in 2003 and SARS-CoV-2 caused the ongoing COVID-19 pandemic. Both viruses are most likely originated from bats. Thus, direct or indirect inter-species transmission from bats to humans is required for the viruses to cause pandemics. Receptor utilization is a key factor determining the host range of viruses which is critical to the inter-species transmission. Angiotensin-converting enzyme 2 (ACE2) is the receptor of both SARS-CoV and SARS-CoV-2, but only ACE2s of certain animals can be utilized by the viruses. Here, we employed pseudovirus cell-entry assay to evaluate the receptor-utilizing capability of ACE2s of 20 animals by the two viruses and found that SARS-CoV-2 utilized less ACE2s than SARS-CoV, indicating a narrower host range of SARS-CoV-2. Especially, SARS-CoV-2 tended not to use murine or non-mammal ACE2s. Meanwhile, pangolin-CoV, another SARS-related coronavirus highly homologous to SARS-CoV-2 in its genome, yet showed similar ACE2 utilization profile with SARS-CoV rather than SARS-CoV-2. Nevertheless, the actual susceptibility of these animals to the coronaviruses should be further verified by in vivo studies. To clarify the mechanism underlying the receptor utilization, we compared the amino acid sequences of the 20 ACE2s and found 5 amino acid residues potentially critical for ACE2 utilization, including the N-terminal 20th and 42nd amino acid residues that might determine the different receptor utilization of SARS-CoV, SARS-CoV-2 and pangolin-CoV. Our studies enhance the understanding of receptor utilization of pandemic coronaviruses, potentially contributing to the virus tracing, intermediate host screening and epidemic prevention for pathogenic coronaviruses.

15.
Infect Drug Resist ; 13: 2053-2061, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636658

RESUMO

Purpose: Although immune dysfunction has been investigated in adult septic patients, early immune status remains unclear. In this study, our primary aim was to assess early immune status in adult patients with sepsis stratified by age and its relevance to hospital mortality. Patients and Methods: A post hoc analysis of a multicenter, randomized controlled trial was conducted; 273 patients whose immune status was evaluated within 48 hours after onset of sepsis were enrolled. Early immune status was evaluated by the percentage of monocyte human leukocyte antigen-DR (mHLA-DR) in total monocytes within 48 hours after onset of sepsis and it was classified as immunoparalysis (mHLA-DR ≤30%) or non-immunoparalysis (>30%). Three logistic regression models were conducted to explore the associations between early immunoparalysis and hospital mortality. We also developed two sensitivity analyses to find out whether the definition of early immune status (24 hours vs 48 hours after onset of sepsis) and immunotherapy affect the primary outcome. Results: Of the 181 elderly (≥60yrs) and 92 non-elderly (<60yrs) septic patients, 71 (39.2%) and 25 (27.2%) died in hospital, respectively. The percentage of early immunoparalysis in the elderly was twice of that in the non-elderly patients (32% vs 16%, p=0.006). For the elderly, hospital mortality was higher in the immunoparalysis ones than the non-immunoparalysis ones (53.4% vs 32.5%, p=0.009). But there was no significant difference in hospital mortality between immunoparalysis non-elderly patients and non-immunoparalysis non-elderly ones (33.5% vs 26.0%, p=0.541). By means of logistic regression models, we found that early immunoparalysis was independently associated with increased hospital mortality in elderly, but not in non-elderly patients. Sensitivity analysis further confirmed the definition of early immune status and immunotherapy did not affect the outcomes. Conclusion: The elderly were more susceptible to early immunoparalysis after onset of sepsis. Early immunoparalysis was independently associated with poor prognosis in elderly, but not in non-elderly patients.

16.
Turk J Gastroenterol ; 31(6): 474-481, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32721919

RESUMO

BACKGROUND/AIMS: Intraoperative blood loss more than 400 mL during gastrointestinal surgery is an independent predictor of mortality. Desmopressin acetate (DDAVP) could reduce perioperative blood loss. Few studies have prompted concerning the effects of DDAVP on gastrointestinal surgery. This study was to investigate whether DDAVP can decrease blood loss in patients with massive hemorrhage undergoing gastrointestinal surgery. MATERIALS AND METHODS: A multiple-centers, double-blind clinical trial was conducted, patients who underwent gastrointestinal surgery were recruited from 3 hospitals, randomly assigned to two different groups. Patients in the treatment group received desmopressin 0.3 ug/kg,30 min once a day after surgery, patients in the control group received 50 ml saline for 30 min. The primary outcome was the changes of hemoglobin at 24 hours after the surgery. And the secondary outcomes included coagulation function, urine volume, serum creatinine, and safety. RESULTS: There were 59 patients enrolled between 1 June 2015 and 1 June 2017. At 24hr.after surgery, a decrease in hemoglobin in the DDAVP group was significantly lower than that in the NS group (-5.0±6.9 g/L vs. -10.2±9.3g/L, p=0.03). Sonoclot® showed that the platelet function in the DDAVP group was higher than that in NS group at 24 hr. (2.56 ±0.59 vs. 1.91 ±0.72, p<0.05). There was no difference in urine volume and serum creatinine at 24 hr. between two group. CONCLUSION: DDAVP could reduce post-operation blood loss in patients with massive hemorrhage undergoing surgery by improving the platelet function. We observed no difference in urine volume and serum creatinine in two groups.

17.
Vector Borne Zoonotic Dis ; 20(10): 755-762, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32679008

RESUMO

As one of the important tick-borne zoonotic pathogens, Anaplasma has both veterinary and public health significance. Here, we performed a survey of Anaplasma infection in the goats from a farm in Beijing, China, and found 44.6% (41/92) were infected with Anaplasma capra, and 22.8% (21/92) were infected with Anaplasma sp. This Anaplasma sp. bacterium was close to a recently emerging Anaplasma platys strain based on gltA and groEL gene phylogenetic analysis. As to further understand the characteristics of Anaplasma sp., we raised a couple of positive goats (n = 2) in the laboratory with tick-free settings. We observed inappetence, vomiting, high fever, and weakness of limbs in the goat's offspring (n = 3). In addition, the blood samples from all offspring were all positive of this Anaplasma spp. We did not see any intracellular morulae in neutrophils, monocytes, and erythrocytes, but we identified some in the platelets of the blood smears from the positive goats by light microscopy. We named it A. platys-like and suggested it may infect platelets and be transmitted vertically through the placenta of goats. These findings deserve further evaluation.

18.
Open Forum Infect Dis ; 7(6): ofaa128, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32523970

RESUMO

Background: Hematogenous dissemination of Talaromyces marneffei can result in multiorgan involvement (skin, lung, and reticuloendothelial system involvement); however, few studies have reported intestinal T marneffei infections. We investigated clinical features, management, and patient outcomes concerning Talaromyces-related intestinal infections. Methods: Patients with Talaromycosis between August 2012 and April 2019 at The First Affiliated Hospital of Guangxi Medical University, China, were retrospectively analyzed. Patients presenting with intestinal Talaromycosis and endoscopy-confirmed diagnoses were investigated. We also undertook a systematic review of the relevant English and Chinese literature. Results: Of 175 patients diagnosed with Talaromycosis, 33 presented with gastrointestinal symptoms, and 31 underwent stool cultures, 1 of which tested positive. Three patients had gastrointestinal symptoms and negative stool cultures, and endoscopic tissue biopsy confirmed a pathological diagnosis. A systematic review of 14 reports on human Talaromycosis identified an additional 16 patients. Fever, weight loss, and anemia were the most common symptoms, along with abdominal pain, diarrhea, and bloody stools. Abdominal computed tomography showed intestinal wall edema and thickening and/or abdominal lymphadenopathy. Endoscopy showed erosion, hyperemia, edema, and multiple intestinal mucosal ulcers. Of the 19 patients, 16 received antifungal therapy, 14 of whom recovered and 2 died. Three patients received no therapy and died. Conclusions: Gastrointestinal disseminated Talaromycosis is not rare and can affect the stomach, duodenum, and colon, and may involve the entire digestive tract. Colon is the most common site. Endoscopy is needed for patients presenting with gastrointestinal symptoms in T marneffei-infected endemic areas. Systemic application of effective antifungal therapy can improve the prognosis.

19.
Virus Res ; 286: 198074, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32589897

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus causing the pandemic of severe pneumonia (Coronavirus Disease 2019, COVID-19). SARS-CoV-2 is highly pathogenic in human, having posed immeasurable public health challenges to the world. Innate immune response is critical for the host defense against viral infection and the dysregulation of the host innate immune responses probably aggravates SARS-CoV-2 infection, contributing to the high morbidity and lethality of COVID-19. It has been reported that some coronavirus proteins play an important role in modulating innate immunity of the host, but few studies have been conducted on SARS-CoV-2. In this study, we screened the viral proteins of SARS-CoV-2 and found that the viral ORF6, ORF8 and nucleocapsid proteins were potential inhibitors of type I interferon signaling pathway, a key component for antiviral response of host innate immune. All the three proteins showed strong inhibition on type I interferon (IFN-ß) and NF-κB-responsive promoter, further examination revealed that these proteins were able to inhibit the interferon-stimulated response element (ISRE) after infection with Sendai virus, while only ORF6 and ORF8 proteins were able to inhibit the ISRE after treatment with interferon beta. These findings would be helpful for the further study of the detailed signaling pathway and unveil the key molecular player that may be targeted.


Assuntos
Betacoronavirus/genética , Interações Hospedeiro-Patógeno/genética , Interferon beta/genética , NF-kappa B/genética , Proteínas do Nucleocapsídeo/genética , Proteínas Virais/genética , Betacoronavirus/imunologia , Regulação da Expressão Gênica , Genes Reporter , Células HEK293 , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Interferon beta/imunologia , Luciferases/genética , Luciferases/metabolismo , NF-kappa B/imunologia , Proteínas do Nucleocapsídeo/imunologia , Fosfoproteínas , Plasmídeos/química , Plasmídeos/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Elementos de Resposta , Vírus Sendai/genética , Vírus Sendai/imunologia , Transdução de Sinais , Transfecção/métodos , Proteínas Virais/imunologia
20.
BMC Infect Dis ; 20(1): 394, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493232

RESUMO

BACKGROUND: Talaromyces marneffei is a highly pathogenic fungus that can cause life-threatening fatal systemic mycosis. Disseminated Talaromycosis marneffei affects multiple organs, including the lungs, skin, and reticuloendothelial system. However, T. marneffei infection has rarely been reported in human immunodeficiency virus (HIV)-negative infants with multiple intestinal perforations and diffuse hepatic granulomatous inflammation. CASE PRESENTATION: We present the case of an HIV-negative 37-month-old boy who has had recurrent pneumonia since infancy and was infected with disseminated Talaromycosis. Contrast-enhanced computed tomography of the whole abdomen showed hepatomegaly and intestinal wall thickening in the ascending colon and cecum with mesenteric lymphadenopathy. Colonoscopy showed a cobblestone pattern with erosion, ulcer, polypoid lesions, and lumen deformation ranging from the colon to the cecum. T. marneffei was isolated from the mucous membrane of the colon, liver, and bone marrow. After antifungal treatment and surgery, his clinical symptoms significantly improved. Whole-exome sequencing using the peripheral blood of the patient and his parents' revealed a heterozygous missense mutation in exon 17 of the STAT3 gene (c.1673G>A, p.G558D). CONCLUSIONS: In T. marneffei infection-endemic areas, endoscopic examination, culture, or histopathology from the intestine tissue should be performed in disseminated Talaromycosis patients with gastrointestinal symptoms. Timely and systemic antifungal therapy could improve the prognosis. Immunodeficiency typically should be considered in HIV-negative infants with opportunistic infections.


Assuntos
Hepatopatias/diagnóstico , Micoses/diagnóstico , Fator de Transcrição STAT3/genética , Talaromyces/isolamento & purificação , Antifúngicos/uso terapêutico , Pré-Escolar , Colonoscopia , Diagnóstico Diferencial , Humanos , Mucosa Intestinal/microbiologia , Perfuração Intestinal , Hepatopatias/tratamento farmacológico , Hepatopatias/microbiologia , Masculino , Mutação de Sentido Incorreto , Micoses/tratamento farmacológico , Micoses/microbiologia , Tomografia Computadorizada por Raios X
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