Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 95
Filtrar
1.
Nat Commun ; 15(1): 2381, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493178

RESUMO

Candida auris has become a serious threat to public health. The mechanisms of how this fungal pathogen adapts to the mammalian host are poorly understood. Here we report the rapid evolution of an adaptive C. auris multicellular aggregative morphology in the murine host during systemic infection. C. auris aggregative cells accumulate in the brain and exhibit obvious advantages over the single-celled yeast-form cells during systemic infection. Genetic mutations, specifically de novo point mutations in genes associated with cell division or budding processes, underlie the rapid evolution of this aggregative phenotype. Most mutated C. auris genes are associated with the regulation of cell wall integrity, cytokinesis, cytoskeletal properties, and cellular polarization. Moreover, the multicellular aggregates are notably more recalcitrant to the host antimicrobial peptides LL-37 and PACAP relative to the single-celled yeast-form cells. Overall, to survive in the host, C. auris can rapidly evolve a multicellular aggregative morphology via genetic mutations.


Assuntos
Candidíase , Sepse , Animais , Camundongos , Candida/genética , Candidíase/microbiologia , Candida auris , Saccharomyces cerevisiae , Fenótipo , Antifúngicos , Testes de Sensibilidade Microbiana , Mamíferos
2.
Emerg Microbes Infect ; 13(1): 2302843, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38238874

RESUMO

The emerging human fungal pathogen Candida auris has become a serious threat to public health. This pathogen has spread to 10 provinces in China as of December 2023. Here we describe 312 C. auris-associated hospitalizations and 4 outbreaks in healthcare settings in China from 2018 to 2023. Three genetic clades of C. auris have been identified during this period. Molecular epidemiological analyses indicate that C. auris has been introduced and local transmission has occurred in multiple instances in China. Most C. auris isolated from China (98.7%) exhibited resistance to fluconazole, while only a small subset of strains were resistant to amphotericin B (4.2%) and caspofungin (2.2%).


Assuntos
Antifúngicos , Candidíase , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida , Candidíase/microbiologia , Candida auris , Surtos de Doenças , China/epidemiologia , Testes de Sensibilidade Microbiana
3.
Water Res ; 249: 120735, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38007898

RESUMO

Phosphonate used as scale inhibitor is a non-negligible eutrophic contaminant in corresponding polluted waters. Besides, its conversion to orthophosphate (ortho-P) is a precondition for realizing bioavailable phosphorus recovery. Due to the feeble degradation efficiency with less than 30 % from classical Fenton commonly used in industrial wastewater treatment and itself vulnerable to strong inhibition interference of matrix chloride ions, we proposed an electrochemical approach to transform the native salt in the solution into oxidizing substances, sort of achieving beneficial utilization of matrix waste, and enhanced the ortho-P conversion rate of 1-Hydroxyethane-1,1-diphosphonic acid (HEDP) to 89.2 % (± 3.6 %). In electrochlorination system, it was found that HEDP rapidly complexed with Fe(II) and then coordinated in-situ Fe(III) to release free HEDP via intramolecular metal-ligand electron transfer reaction. The subsequent degradation mainly rooted in the oxidation of pivotal reactive species HClO, FeIVO2+ and 1O2, causing C-P and CC bonds to fracture in sequence. Eventually the organically bound phosphorus of HEDP was recovered as ortho-P. This study acquainted the audiences with the rare mechanism of chloridion-triggered HEDP degradation under electrochemical way, as well as offered a feasible technology for synchronous transformation of organically bound phosphorus to ortho-P and elimination from phosphonates.


Assuntos
Organofosfonatos , Poluentes Químicos da Água , Fosfatos , Compostos Férricos , Ácido Etidrônico , Oxirredução , Fósforo , Poluentes Químicos da Água/análise , Peróxido de Hidrogênio/química
4.
Int J Antimicrob Agents ; 62(6): 107010, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37863341

RESUMO

OBJECTIVES: Infections caused by azole-resistant Candida tropicalis strains are increasing in clinical settings. The reason for this epidemical change and the mechanisms of C. tropicalis azole resistance are not fully understood. METHODS: In this study, we performed biological and genomic analyses of 239 C. tropicalis strains, including 115 environmental and 124 human commensal isolates. RESULTS: Most (99.2%) of the isolates had a baseline diploid genome. The strains from both environmental and human niches exhibit similar abilities to survive under stressful conditions and produce secreted aspartic proteases. However, the human commensal isolates exhibited a stronger ability to filament than the environmental strains. We found that 19 environmental isolates (16.5%) and 24 human commensal isolates (19.4%) were resistant to fluconazole. Of the fluconazole-resistant strains, 37 isolates (86.0%) also exhibited cross-resistance to voriconazole. Whole-genome sequencing and phylogenetic analyses revealed that both environmental and commensal isolates were widely distributed in a number of genetic clusters, but the two populations exhibited a close genetic association. The majority of fluconazole-resistant isolates were clustered within a single clade (X). CONCLUSIONS: The combination of hotspot mutations (Y132F and S154F) and genomic expansion of ERG11, which encodes the azole target lanosterol 14-α-demethylase and represents a major target of azole drugs, was a major mechanism for the development of azole resistance. The isolates carrying both hotspot mutations and genomic expansion of ERG11 exhibited cross-resistance to fluconazole and voriconazole. Moreover, the azole-resistant isolates from both the environmental and human commensal niches showed similar genotypes.


Assuntos
Azóis , Fluconazol , Humanos , Fluconazol/farmacologia , Azóis/farmacologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Voriconazol/farmacologia , Candida tropicalis/genética , Filogenia , Mutação , Genômica , Farmacorresistência Fúngica/genética , Testes de Sensibilidade Microbiana , Proteínas Fúngicas/genética
5.
Emerg Infect Dis ; 29(7): 1425-1428, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37347816

RESUMO

Candida vulturna belongs to the Candida haemulonii species complex and is phylogenetically related to C. auris. We report a C. vulturna outbreak among persons in Shanxi Province, China, during 2019-2022. Isolates were resistant to multiple antifungal drugs and exhibited enhanced adhesion and biofilm formation properties.


Assuntos
Candida , Candidíase , Candidíase/epidemiologia , Candidíase/microbiologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , China/epidemiologia , Testes de Sensibilidade Microbiana
6.
Anim Nutr ; 13: 229-239, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37168447

RESUMO

The aim of this study was to examine the effects of dietary protein and lipid levels on the growth performance and homeostasis of the intestinal flora in Paramisgurnus dabryanus. An 8-wk 3 × 3 two-factorial experiment was conducted to investigate the interaction between dietary crude protein (CP: 30%, 35%, 40%) and ether extract (EE: 6%, 10%, 14%) on the growth rate and the intestinal microflora of P. dabryanus. A total of 2,160 fish (5.19 ± 0.01 g) were randomly allotted to 36 aquariums each with 60 fish. Fish were fed the experimental diet twice daily. Results revealed that weight gain rate (WGR), specific growth rate (SGR), protein efficiency ratio and net protein utilization significantly increased when increasing protein levels from 30% to 40% (P < 0.05). Both WGR and SGR enhanced first but reduced thereafter with maximum value at 10% lipid level as dietary lipid increased from 6% to 14% (P < 0.05). Significant interactions between protein and lipid were found with feed conversion rate, lipid efficiency ratio and net lipid utilization (P < 0.05). At the phylum level, Proteobacteria and Actinobacteria were the dominant bacteria; at the genus level, Burkholderia-Caballeronia-Paraburkholderia was the dominant bacteria. Fish fed the diet containing 10% lipid had a higher abundance of Proteobacteria and unclassified_f_Eenterobacteriaceae than those fed the 14% lipid diet, and a higher abundance of Rhodobacter than those fed the 6% lipid diet (P < 0.05). Analysis of the predicted functions showed that metabolism in the intestine of fish in the CP40EE10 group was more active than that in CP30EE14 group. Polynomial regression analysis found that a diet containing 40.87% protein and 9.88% lipid can be considered optimal for P. dabryanus.

7.
Sci China Life Sci ; 66(8): 1915-1929, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37118508

RESUMO

Sexual reproduction is prevalent in eukaryotic organisms and plays a critical role in the evolution of new traits and in the generation of genetic diversity. Environmental factors often have a direct impact on the occurrence and frequency of sexual reproduction in fungi. The regulatory effects of atmospheric relative humidity (RH) on sexual reproduction and pathogenesis in plant fungal pathogens and in soil fungi have been extensively investigated. However, the knowledge of how RH regulates the lifecycles of human fungal pathogens is limited. In this study, we report that low atmospheric RH promotes the development of mating projections and same-sex (homothallic) mating in the human fungal pathogen Candida albicans. Low RH causes water loss in C. albicans cells, which results in osmotic stress and the generation of intracellular reactive oxygen species (ROS) and trehalose. The water transporting aquaporin Aqy1, and the G-protein coupled receptor Gpr1 function as cell surface sensors of changes in atmospheric humidity. Perturbation of the trehalose metabolic pathway by inactivating trehalose synthase or trehalase promotes same-sex mating in C. albicans by increasing osmotic or ROS stresses, respectively. Intracellular trehalose and ROS signal the Hog1-osmotic and Hsf1-Hsp90 signaling pathways to regulate the mating response. We, therefore, propose that the cell surface sensors Aqy1 and Gpr1, intracellular trehalose and ROS, and the Hog1-osmotic and Hsf1-Hsp90 signaling pathways function coordinately to regulate sexual mating in response to low atmospheric RH conditions in C. albicans.


Assuntos
Candida albicans , Proteínas Fúngicas , Humanos , Candida albicans/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Trealose/metabolismo , Umidade , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia , Reprodução/fisiologia
8.
Ann Transl Med ; 11(6): 251, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37082678

RESUMO

Background: Previous prediction models for postoperative stress urinary incontinence (SUI) cannot be applied to patients receiving transvaginal mesh (TVM) surgery and colpocleisis or those with preoperative subject urinary incontinence. This study aimed to develop and validate a new machine learning model and compare it to previous models. Methods: Female patients who underwent prolapse surgeries for stage 2-4 anterior or apical prolapse between January 1, 2015, and December 31, 2019, at Peking Union Medical College Hospital were enrolled. Prolapse surgeries included native tissue repair, LeFort/colpocleisis, sacrocolpopexy, and TVM surgery. The existing models to predict postoperative SUI were externally validated. Subsequently, the dataset was randomly divided into 2 sets in a 4:1 ratio. The larger group was used to construct and internally validate models of logistic regression, random forest, and extreme gradient boosting (XGBoost), which were then externally validated. The discrimination of the prediction models was evaluated using the area under the curve, while the calibration of the models was measured using the Spiegelhalter z test, mean absolute error (MSE), and calibration curves. Results: Overall, 555 patients were enrolled, and 116 experienced SUI 1 year postoperatively. Previous logistic models had poor performance, with areas under the curve of 0.544 and 0.586. In the model construction, the areas under the curve were 0.595, 0.842, and 0.714 for the logistic, random forest, and XGBoost models, respectively. However, only the XGBoost model exhibited good discrimination and calibration for both internal and external validations. Body mass index (BMI), C point of pelvic organ prolapse (POP) quantification stage, age, Aa point of POP quantification stage, and TVM surgery were the 5 most important predictors of postoperative SUI in the XGBoost model. Conclusions: Previous models had poor discrimination and calibration among a Chinese population. Hence, we developed and validated an XGBoost model, which performed well irrespective of the preoperative subjective urinary incontinence (preUI) and surgical methods. Further validation is still required.

9.
Nat Commun ; 14(1): 2067, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-37045865

RESUMO

The human fungal pathogen Candida albicans can switch stochastically and heritably between a "white" phase and an "opaque" phase. Opaque cells are the mating-competent form of the species, whereas white cells are thought to be essentially "sterile". Here, we report that glucose depletion, a common nutrient stress, enables C. albicans white cells to undergo efficient sexual mating. The relative expression levels of pheromone-sensing and mating-associated genes (including STE2/3, MFA1, MFα1, FIG1, FUS1, and CEK1/2) are increased under glucose depletion conditions, while expression of mating repressors TEC1 and DIG1 is decreased. Cph1 and Tec1, factors that act downstream of the pheromone MAPK pathway, play opposite roles in regulating white cell mating as TEC1 deletion or CPH1 overexpression promotes white cell mating. Moreover, inactivation of the Cph1 repressor Dig1 increases white cell mating ~4000 fold in glucose-depleted medium relative to that in the presence of glucose. Our findings reveal that the white-to-opaque epigenetic switch may not be a prerequisite for sexual mating in C. albicans in nature.


Assuntos
Candida albicans , Proteínas Fúngicas , Humanos , Candida albicans/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Reprodução/fisiologia , Feromônios/genética , Feromônios/metabolismo , Epigênese Genética , Regulação Fúngica da Expressão Gênica , Genes Fúngicos Tipo Acasalamento/genética
10.
Materials (Basel) ; 16(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37048849

RESUMO

Submicron-sized quasi-spherical zinc oxide (ZnO) particles were prepared by wet ultrafine grinding in a stirred media mill under various conditions. The effects of parameters (i.e., solution type, acid or alkali concentration, solid content and grinding time) on the particle median size (d50), particle size distribution (PSD) and sphericity of ZnO particles was investigated. The results show that submicron-sized quasi-spherical particles (i.e., d50: 370 nm, uniformity coefficient (n) of 2.28 and sphericity of 0.91) can be obtained when the micron-sized ZnO particles are ground for 30 min in a CH3COOH solution at a concentration of 0.010 mol/L with 20 wt.% of solid content. The chemical dissolution of ZnO particles ground in the presence and absence of acetic acid is discussed. It is indicated that chemical dissolution accelerated due to the mechanochemical effects could reduce the particle size, obtain a narrower PSD and enhance the sphericity. In addition, the functions of selection and breakage were used to analyze the grinding mechanism of ZnO particles.

11.
PLoS Pathog ; 19(3): e1011239, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36913408

RESUMO

Candida auris is an emerging multidrug-resistant fungal pathogen and a new global threat to human health. A unique morphological feature of this fungus is its multicellular aggregating phenotype, which has been thought to be associated with defects in cell division. In this study, we report a new aggregating form of two clinical C. auris isolates with increased biofilm forming capacity due to enhanced adherence of adjacent cells and surfaces. Unlike the previously reported aggregating morphology, this new aggregating multicellular form of C. auris can become unicellular after treatment with proteinase K or trypsin. Genomic analysis demonstrated that amplification of the subtelomeric adhesin gene ALS4 is the reason behind the strain's enhanced adherence and biofilm forming capacities. Many clinical isolates of C. auris have variable copy numbers of ALS4, suggesting that this subtelomeric region exhibits instability. Global transcriptional profiling and quantitative real-time PCR assays indicated that genomic amplification of ALS4 results in a dramatic increase in overall levels of transcription. Compared to the previously characterized nonaggregative/yeast-form and aggregative-form strains of C. auris, this new Als4-mediated aggregative-form strain of C. auris displays several unique characteristics in terms of its biofilm formation, surface colonization, and virulence.


Assuntos
Antifúngicos , Candida , Humanos , Candida/genética , Candida auris , Biofilmes , Genômica , Testes de Sensibilidade Microbiana
12.
Materials (Basel) ; 16(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36770300

RESUMO

Three sodium polyacrylate copolymers PD0x (Poly acrylic acid-co-sodium 4-vinylbenzenesulfonate or PD01; Poly acrylic acid-co-sodium 4-vinylbenzenesulfonate-co-hydroxyethyl methacrylate or PD02 and Poly methyl methacrylate-co-acrylic acid-co-sodium 4-vinylbenzenesulfonate-co-hydroxyethyl methacrylate or PD03) were synthesized as water-based dispersants for grinding red-brown pigment ZnFe1.2Cr0.8O4 particles prepared by the solid phase method (S-ZnF). The particle size distribution, viscosity of suspensions, and adsorption capacity of dispersants were explored by laser particle size analysis, viscometer, and thermogravimetry (TG), respectively. The application of 2 wt.% dispersant PD02 in the S-ZnF suspension ground for 90 min can deliver a finer product with the narrower particle size distribution. The added dispersant PD02 in the grinding process of the S-ZnF particles exhibits a suitable viscosity of the suspension and generates more hydrogen bonds on the S-ZnF particle surface. The sulfonic acid groups (SO3-) and carboxylic acid groups (-COO-) in the dispersant PD02 can also provide a strong charge density, which is favorable for the dispersion and grinding of the S-ZnF particles in the suspensions. Furthermore, the adsorption behavior of polymeric dispersant PD02 adsorbed on the S-ZnF particles surface was simulated and analyzed by adsorption thermodynamic models and adsorption kinetic models. It is indicated that the adsorption thermodynamic behavior of dispersant PD02 adsorbed on the S-ZnF particles surface follows the Langmuir model, and the adsorption process is endothermic and a random process with increased confusion during the grinding process. In addition, the adsorption kinetics of dispersant PD02 adsorbed on the S-ZnF particles surface are more in line with the pseudo-first-order kinetic models. Therefore, the adsorption process of dispersant PD02 on the S-ZnF particles surface can be considered as a single-surface adsorption process.

14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(5): 768-772, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36325772

RESUMO

Objective To explore the feasibility and efficacy of the training program for aromatherapy in palliative care. Methods Data from four aromatherapy training programs held at Peking Union Medical College Hospital from 2016 to 2019 was collected.The feasibility and efficacy of the training were measured based on the self-reported questionnaires from 120 trainees. Results A total of 56 valid questionnaires were collected.The total score of the programs was 8.09.Trainees reported that the program enriched theoretical knowledge and enhanced practical confidence.After the training,79.6% of the trainees carried out aromatherapy in practice,while those who failed to practice were mainly due to the lack of appropriate opportunities.Some trainees suggested adding more practice hours and hoped to get follow-up guidance on a case-by-case basis. Conclusions It is feasible to carry out the short-term training program of aromatherapy in palliative care,which can enrich trainees' theoretical knowledge and enhance the practical confidence.It is necessary to provide continuous guidance after training to increase the proportion of trainees adopting aromatherapy in palliative care practice.


Assuntos
Aromaterapia , Cuidados Paliativos , Humanos , Estudos de Viabilidade , Inquéritos e Questionários
15.
Front Oncol ; 12: 1003722, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212485

RESUMO

Background: Approximately 20% of patients with lung cancer would experience postoperative cardiopulmonary complications after anatomic lung resection. Current prediction models for postoperative complications were not suitable for Chinese patients. This study aimed to develop and validate novel prediction models based on machine learning algorithms in a Chinese population. Methods: Patients with lung cancer receiving anatomic lung resection and no neoadjuvant therapies from September 1, 2018 to August 31, 2019 were enrolled. The dataset was split into two cohorts at a 7:3 ratio. The logistic regression, random forest, and extreme gradient boosting were applied to construct models in the derivation cohort with 5-fold cross validation. The validation cohort accessed the model performance. The area under the curves measured the model discrimination, while the Spiegelhalter z test evaluated the model calibration. Results: A total of 1085 patients were included, and 760 were assigned to the derivation cohort. 8.4% and 8.0% of patients experienced postoperative cardiopulmonary complications in the two cohorts. All baseline characteristics were balanced. The values of the area under the curve were 0.728, 0.721, and 0.767 for the logistic, random forest and extreme gradient boosting models, respectively. No significant differences existed among them. They all showed good calibration (p > 0.05). The logistic model consisted of male, arrhythmia, cerebrovascular disease, the percentage of predicted postoperative forced expiratory volume in one second, and the ratio of forced expiratory volume in one second to forced vital capacity. The last two variables, the percentage of forced vital capacity and age ranked in the top five important variables for novel machine learning models. A nomogram was plotted for the logistic model. Conclusion: Three models were developed and validated for predicting postoperative cardiopulmonary complications among Chinese patients with lung cancer. They all exerted good discrimination and calibration. The percentage of predicted postoperative forced expiratory volume in one second and the ratio of forced expiratory volume in one second to forced vital capacity might be the most important variables. Further validation in different scenarios is still warranted.

16.
Genes Genomics ; 44(12): 1487-1498, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36244041

RESUMO

BACKGROUND: Holothuria scabra is a costly gourmet and traditional Chinese tonic medicine. However, the lack of high-quality genome information hinders the genetic, phylogenetic, and bioactivator researches. OBJECTIVE: To construct high-quality genomic data of H. scabra and conduct genome-wide phylogenetic analysis. METHODS: The whole genome of a male H. scabra was sequenced based on Nanopore MinION platform, and the sequence was assembled by wtdbg2. Transcriptome sequencing was used to aid the gene annotation. Repeat sequences, non-coding RNA, pseudogene and gene functional annotation were analyzed. 750 single-copy gene families from ten species were applied to construct phylogenetic tree for evolutionary analysis by using the ML method. RESULTS: The H. scabra genome of 1.18 Gb (N50 = 1557,492 bp) with 500.42 Mb of putative repetitive sequences was assembled from a male H. scabra individual, and 16,642 protein-coding genes, 951 pseudogenes, 1791 motifs and 45,400 domains from the generated assembly were identified. The divergence time between H. scabra and its ancestor was estimated approximately 192.6 million years ago. H. scabra and A. japonicas joined together while sea urchin and sea star diverged about 440 Mya ago. Some key genes involved in notochord and gill slits development, skeleton degeneration and nervous system, as well as homeobox genes differ between H. scabra and Apostichopus japonicas. CONCLUSION: We report the first whole genome of H. scabra with expectation that this will be a valuable resource for genetic, phylogenetic, breading, molecular biology and bioactivator studies of sea cucumbers and other invertebrates.


Assuntos
Holothuria , Sequenciamento por Nanoporos , Nanoporos , Animais , Holothuria/genética , Filogenia , Anotação de Sequência Molecular
17.
Transl Cancer Res ; 11(7): 1880-1888, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36249886

RESUMO

Background: Oxaliplatin induces splenomegaly, which can cause blood sequestration and relevant cytopenia, leading to further dose reductions and schedule modifications of chemotherapy. Here, we aimed to explore the changes of spleen volume induced by oxaliplatin as well as its impact on blood parameters and anti-neoplastic treatment in patients with colon cancer. Methods: We conducted a retrospective analysis of patients with resectable stage II-IV colon cancer who were treated with oxaliplatin and capecitabine at our institution from January 2016 to December 2017. Laboratory tests and computed tomographic (CT) data before, during and up to 18 months after the end of chemotherapy were extracted. Spleen volume was determined by volumetric measurements. Splenomegaly was defined as an over 30% increase in spleen volume from baseline. Results: Out of 144 patients, 102 patients (70.8%) developed splenomegaly, and 75 (73.5%) recovered at 18 months after the end of chemotherapy. Higher cumulative dose intensity of oxaliplatin (P=0.001) and higher baseline platelet count (P=0.045) were risk factors associated with splenomegaly. Compared to those without splenomegaly, splenomegaly patients experienced more severe reduction in platelet (P<0.001), erythrocyte (P=0.010), neutrophil (P=0.002) and lymphocyte (P=0.006) counts and were more likely to undergo dose reductions of oxaliplatin (21.6% vs. 7.1%, P=0.038) as well as interruptions of chemotherapy (18.6% vs. 4.8%, P=0.040) due to thrombocytopenia. Conclusions: Splenomegaly was a common and partly irreversible side effect of oxaliplatin-based therapy in patients with colon cancer. It is correlated with more severe pancytopenia and might exert a negative impact on the efficacy of anti-neoplastic treatment.

18.
Front Bioeng Biotechnol ; 10: 965769, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35942007

RESUMO

There is a need to improve the efficacy and safety of endovascular techniques in venous thrombotic diseases, and microbubble enhanced sonothrombolysis is a promising approach. However, whether endovascular low-frequency ultrasound (LFUS) can be utilized in microbubble enhanced sonothrombolysis is unclear. Here, we present a catheter-based thrombolytic system that combines unfocused low-frequency low-intensity ultrasound with novel fibrin-targeted drug-loaded bifunctional microbubbles. We develop an in vitro flow model and an in vivo rabbit inferior vena cava (IVC) thrombosis model to evaluate the safety and efficacy of the thrombolytic system. The results indicate that microbubble enhanced sonothrombolysis with endovascular LFUS treatment for 30 min is equally effective compared to pure pharmacologic treatment. Furthermore, the thrombolytic efficacy of this system is safely and substantially improved by the introduction of a fibrin-targeted drug-loaded bifunctional microbubble with a reduction of the fibrinolytic agent dosage by 60%. The microbubble enhanced endovascular LFUS sonothrombolysis system with excellent thrombolytic efficacy may serve as a new therapeutic approach for venous thrombotic diseases.

19.
mSphere ; 7(4): e0026022, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-35727043

RESUMO

The human fungal pathogen Candida glabrata is phylogenetically closely related to Saccharomyces cerevisiae, a model eukaryotic organism. Unlike S. cerevisiae, which has both haploid and diploid forms and a complete sexual cycle, C. glabrata has long been considered a haploid and asexual species. In this study, we analyzed the ploidy states of 500 clinical isolates of C. glabrata from four Chinese hospitals and found that approximately 4% of the isolates were in or able to spontaneously switch to an aneuploid (genomic DNA, 1N-2N), diploid (2N), or hyperdiploid (>2N) form under in vivo or in vitro conditions. Stable diploid cells were identified in 3% of the isolates (15/500). Of particular interest, one clinical strain existed only in the diploid form. Multilocus sequence typing (MLST) assays revealed two major genetic clusters (A and B) of C. glabrata isolates. Most of the isolates (70%) from China belonged to the A cluster, whereas most of the isolates from other countries (such as Iran, Japan, United States, and European countries) belonged to the B cluster. Further investigation indicated that C. glabrata cells of different ploidy forms differed in a number of respects, including morphologies, antifungal susceptibility, virulence, and global gene expression profiles. Additionally, C. glabrata could undergo spontaneous switching between the diploid and haploid forms under both in vitro and in vivo conditions. Given the absence of an apparent sexual phase, one would expect that the ploidy shifts could function as an alternative strategy that promotes genetic diversity and benefits the ability of the fungus to rapidly adapt to the changing environment. IMPORTANCE The human fungal pathogen Candida glabrata has long been thought to be a haploid organism. Here, we report the population structure and ploidy states of 500 clinical isolates of C. glabrata from China. To our surprise, we found that the ploidy of a subset of clinical isolates varied dramatically. Some isolates were in or able to switch to an aneuploid, diploid, or hyperdiploid form. C. glabrata cells with different ploidy differed in a number of biological respects, including morphology, antifungal susceptibility, virulence, and global gene expression profile. Given the absence of an apparent sexual phase in this fungus, we propose that ploidy switching could be a strategy for rapid adaptation to environmental changes and could function as an alternative to sexual reproduction.


Assuntos
Candida glabrata , Diploide , Aneuploidia , Antifúngicos/farmacologia , Candida glabrata/genética , Haploidia , Humanos , Tipagem de Sequências Multilocus , Saccharomyces cerevisiae/genética
20.
Nat Commun ; 13(1): 3553, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729111

RESUMO

Candida auris is a multidrug-resistant human fungal pathogen responsible for nosocomial outbreaks worldwide. Although considerable progress has increased our understanding of the biological and clinical aspects of C. auris, its interaction with the host immune system is only now beginning to be investigated in-depth. Here, we compare the innate immune responses induced by C. auris BJCA001 and Candida albicans SC5314 in vitro and in vivo. Our results indicate that C. auris BJCA001 appears to be less immunoinflammatory than C. albicans SC5314, and this differential response correlates with structural features of the cell wall.


Assuntos
Candida , Candidíase , Antifúngicos/farmacologia , Candida albicans , Candida auris , Candidíase/microbiologia , Humanos , Imunidade Inata , Testes de Sensibilidade Microbiana
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...