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1.
Artigo em Inglês | MEDLINE | ID: mdl-32004095

RESUMO

Objectives: The subxiphoid thoracoscopic approach may be an alternative to the lateral transthoracic approach in the treatment of thymic diseases. This study aimed to assess the safety and efficacy of subxiphoid video-assisted thoracoscopic surgery and compare this approach with the lateral transthoracic variation in terms of short-term perioperative outcomes. Methods: Data for 107 consecutive adult patients who underwent transthoracic or subxiphoid video-assisted thoracic surgery for thymic diseases from July 2015 to February 2019 were retrospectively reviewed. The patients were stratified according to whether they had accompanying myasthenia gravis (MG). Perioperative outcomes were compared between the two cohorts. Results: A total of 107 patients were identified, including 37 patients who underwent subxiphoid video-assisted thoracoscopic thymectomy (S-VATT) and 70 patients who underwent transthoracic video-assisted thoracoscopic thymectomy (T-VATT). The S-VATT group exhibited less operative blood loss (112.14 ± 117.01 versus 58.81 ± 48.67, P = .003), a shorter duration of chest tube usage (3.77 ± 1.83 versus 2.18 ± 1.88, P = .000), lower postoperative pain scores (4.99 ± 0.99 versus 1.57 ± 0.55, P = .000), and a shorter length of postoperative hospital stay (5.83 ± 1.38 versus 4.38 ± 1.26, P = .000) than the T-VATT group. For MG patients, the median operative time was significantly shorter in the S-VATT group than in the T-VATT group (141.46 ± 54.17 versus 95.63 ± 31.25, P = .004). Conclusions: S-VATT is a safe approach for patients with thymic diseases and has potential advantages of a shorter operative time, less intraoperative bleeding, and less postoperative pain compared with the lateral transthoracic approach, especially for patients with MG.

2.
Microb Pathog ; : 104038, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32027976

RESUMO

BACKGROUND AND AIM: PI3Kγ is closely related to inflammation and cardiovascular diseases and thus, PI3Kγ inhibitors are candidate drugs for the treatment of these disorders. Considering the potential effect of the intestinal microbiome on inflammation and cardiovascular diseases, this study aimed to identify characteristics of the intestinal microbial community under PI3Kγ deficiency, to help reveal the potential influence of PI3Kγ inhibitors mediated by the microbial community. METHODS: Exon 2 of the PI3Kγ gene was knocked out in a Balb/c mouse by using single-guide RNAs. Homozygous PI3Kγ-knockout (PI3Kγ-/-) mice were obtained by embryo transfer and hybridization. PI3Kγ-/- and wild-type (WT) mice were raised in the same specific pathogen-free conditions until 8 weeks of age. Then, colonic tissues and feces from the middle segment of the colon were collected and analyzed by Illumina MiSeq sequencing. Differences in intestinal microbial community between the PI3Kγ-/- and WT mice were detected by bioinformatics analysis. RESULTS: The richness and alpha diversity of the colonic microbial community were decreased in PI3Kγ-/- mice. The alpha diversity of the microbial community in feces did not differ between PI3Kγ-/- and WT mice. The beta diversity of the microbial community in feces of PI3Kγ-/- mice was obviously different from that in WT mice, whereas the within-group variation in Bray-Curtis distances of the mucosal microbial community was significantly decreased in PI3Kγ-/- mice. The topological structure of the species-related network of the colonic microbial community in PI3Kγ-/- mice was more polarized. Finally, we predicted that PI3Kγ deficiency might affect the synthesis of some antibiotics, bile acid, and thiamine through effects on the microbial community. CONCLUSIONS: PI3Kγ dysfunction led to degeneration of the intestinal microbial community and might alter the synthesis of some antibiotics, bile acids, and thiamine. The usage of PI3Kγ inhibitors for inflammation and cardiovascular diseases might lead to knock-on effect on our organism through intestinal microbiota.

3.
Obstet Gynecol ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32028490

RESUMO

OBJECTIVE: To compare the odds of a good perinatal outcome between cryopreserved and fresh donor oocytes. METHODS: We used the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System to conduct a retrospective cohort study of women undergoing donor oocyte in vitro fertilization (IVF) from 2012 to 2015. Cycles using cryopreserved embryos, a gestational carrier, or preimplantation genetic testing were excluded. The primary outcome was a good perinatal outcome, defined as a singleton live birth at 37 weeks of gestation or more with birth weight at or within 2,500 g and 4,000 g. Secondary outcomes included live birth, multiple birth, and prematurity. Generalized estimating equation models were used to test the effect of oocyte type on the primary outcome while accounting for covariates and the correlation induced by repeated cycles within a patient. RESULTS: Of the 36,925 cycles included in the analysis, 8,381 (22.7%) used cryopreserved and 28,544 (77.3%) used fresh oocytes. The odds of a good perinatal outcome were marginally but significantly lower with cryopreserved than with fresh oocytes before and after covariate adjustment (22.0% vs 24.1%, unadjusted odds ratio [OR] 0.90, 95% CI 0.85-0.96, adjusted OR 0.88, 95% CI 0.81-0.95). Compared with fresh oocytes, cryopreserved oocytes were associated with lower rates of live birth (39.6% vs 47.7%, OR 0.75, 95% CI 0.72-0.79), multiple birth (22.3% vs 31.2%, OR 0.63, 95% CI 0.58-0.69), and prematurity (27.6% vs 30.6%, OR 0.86, 95% CI 0.79-0.94). CONCLUSION: This retrospective national study demonstrated that the use of cryopreserved compared with fresh donor oocytes in IVF cycles is associated with marginally lower odds of a good perinatal outcome.

4.
Am J Emerg Med ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32037125

RESUMO

BACKGROUND: Corticosteroids have been widely used as adjunct therapy for septic shock for many decades, but both the efficacy and safety remain unclear. The study was designed to investigate overall benefits and potential risks of corticosteroids in immunocompromised patients with septic shock. METHODS: The Medical Information Mart for Intensive Care III (MIMIC-III) database was employed to conduct a cohort study. Immunocompromised patients with septic shock were enrolled and categorized by whether exposure to intravenous corticosteroids. Cox Proportional-Hazards models were used to control for confounders and assess the relationship between corticosteroids use and mortality. RESULTS: A total of 866 patients were enrolled in this study, including 395 in the corticosteroids group and 471 in the non-corticosteroids group. Corticosteroids infusion was not associated with improved 30-day mortality in overall immunocompromised population [34.7% vs 32.1%; adjusted hazard ratio (HR) 1.11, 95% confidence interval (CI) 0.87-1.43, p = 0.37]. The mortality effects were similar in 90-day, 180-day, 1-year and hospital mortality. For the subgroup of patients with metastatic cancer, corticosteroids infusion was associated with a statistically significant increase in the 30-day mortality risk (HR 1.58, 95% CI 1.06-2.37; p = 0.02). Corticosteroids had adverse effects on hemodynamic stability, prolonged ICU and hospital duration, and increased risk of hyperglycemia. CONCLUSIONS: Corticosteroids therapy for the maintenance of blood pressure was not associated with improved mortality or hemodynamic stability in overall immunocompromised population with septic shock. Future randomized clinical trials are required to validate the effects of corticosteroids for septic shock in the special immunocompromised population.

5.
Taiwan J Obstet Gynecol ; 59(1): 43-50, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32039799

RESUMO

OBJECTIVE: Few studies have investigated the long-term impact of synthetic mesh reconstructive surgery for pelvic organ prolapse (POP) on patient outcomes. This study aimed to examine the incidence and risk factors of mesh exposure and the subsequent requirement for surgical interventions due to mesh-related complications. MATERIALS AND METHODS: This retrospective study was conducted from November 2010 to April 2018. We recruited women with Pelvic Organ Prolapse Quantification (POP-Q) stage 3 or 4 who underwent mesh reconstructive surgery for POP, and enrolled 487 women who received transvaginal mesh (TVM) and 110 women who received laparoscopic abdominal sacrocolpopexy (LASC). Assessments included mesh exposure rate and mesh-related complications requiring surgical interventions in both groups. RESULTS: In the LASC group, the overall mesh-related complication rate was 8.18% over a mean follow-up period of 18 months. Concomitant laparoscopic-assisted vaginal hysterectomy was associated with mesh exposure (OR = 9.240; 95% CI = 1.752-48.728). No patients in the concurrent supracervical hysterectomy group were exposed to mesh. In the single-incision TVM group, the overall rate of mesh-related complications was 3.29% over a mean follow-up period of 19 months. Concomitant total vaginal hysterectomy was also a risk factor for mesh exposure (OR = 4.799; 95% CI = 1.313-17.359). CONCLUSION: Preserving the cervix or uterus decreased the rate of mesh exposure in those undergoing TVM and LASC surgery. The overall rate of mesh-related complications was low after up to 8 years of follow-up.

6.
J Clin Invest ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039918

RESUMO

Current antiangiogenic therapy is limited by its cytostatic property, scarce drug delivery to the tumor, and side toxicity. To address these limitations, we unveiled the role of ZEB1, a tumor endothelium-enriched zinc-finger transcription factor, during tumor progression. We discovered that the patients who had lung adenocarcinomas with high ZEB1 expression in tumor endothelium had increased prevalence of metastases and markedly reduced overall survival after the diagnosis of lung cancer. Endothelial ZEB1 deletion in tumor-bearing mice diminished tumor angiogenesis while eliciting persistent tumor vascular normalization by epigenetically repressing TGF-ß signaling. This consequently led to improved blood and oxygen perfusion, enhanced chemotherapy delivery and immune effector cell infiltration, and reduced tumor growth and metastasis. Moreover, targeting vascular ZEB1 remarkably potentiated the anticancer activity of nontoxic low-dose cisplatin. Treatment with low-dose anti-programmed cell death protein 1 (anti-PD-1) antibody elicited tumor regression and markedly extended survival in ZEB1-deleted mice, conferring long-term protective anticancer immunity. Collectively, we demonstrated that inactivation of endothelial ZEB1 may offer alternative opportunities for cancer therapy with minimal side effects. Targeting endothelium-derived ZEB1 in combination with conventional chemotherapy or immune checkpoint blockade therapy may yield a potent and superior anticancer effect.

7.
Sci Total Environ ; 715: 136886, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-32040998

RESUMO

Assessing the impacts of irrigation on water resources is crucial to effectively understanding how water is withdrawn for irrigation purposes. Consequently, the extraction of water from rivers, reservoirs and aquifers for irrigation purposes usually exceeds the net requirement for irrigation due to water lost in its delivery from source to the crop fields. In this this study, we have proposed a model for incorporating seasonal water loss from storage reservoir and conveyance canal into the crop water footprint of irrigated sugarcane. By taking into consideration the duration of seasonal irrigation water release for sugarcane production, we present a method for allocation of blue water footprint using savannah sugar irrigation district as case study. Results have shown that significant volume of water is evaporated seasonally due to irrigation of sugarcane, despite the introduction of an allocation factor to account of evaporation loss to irrigation. For the study period of 2007-2017, the reservoir is the main contributor to water loss by evaporation, it accounts for an average seasonal water loss of 1.1 × 108 m3, followed by evapotranspiration from the crop field 0.26 × 108 m3 and then seepage and evaporation losses from the canal 7.9 × 104 m3. The average seasonal blue water footprint of sugarcane for the period considered is 877 m3/ton which exceeds the global average 209 m3/ton. Plans to expand hectares of cultivated land by the company to boost sugarcane productivity, coupled with the ongoing effort to incorporate hydroelectric power plant to the existing dam to augment electric power supply in the district, will greatly influence the availability water resources in the region. This study highlighted the need for a comprehensive evaluation of water use in irrigated agriculture and may serve as an indicator for optimizing future objectives and strategies associated with water resource planning globally.

8.
Plant Physiol ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054780

RESUMO

Megasporogenesis is a key step during ovule development in angiosperms, but the small number and inaccessibility of these cells have hampered molecular and genome-wide studies. Thus, many questions remain regarding the molecular basis of cell specification, differentiation, and development in the female gametophyte. Here, taking advantage of the correlation between spikelet length and ovule development in rice (Oryza sativa L.), we studied the transcriptome dynamics of young ovules at three stages, the archesporial cell (AC), the megaspore mother cell (MMC) before meiosis, and the functional megaspore (FM) after meiosis, using expression profiling based on RNA-Seq. Our analysis showed that 5,274 genes were preferentially expressed in ovules during megasporogenesis as compared to ovules at the mature female gametophyte stage. Out of these, 958 (18.16%) genes were AC- and/or MMC-preferential genes, and represent a significant enrichment of genes involved in hormone signal transduction and plant-pathogen interaction pathways as well as genes encoding transcription factors. The expression patterns of nine genes that were preferentially expressed in ovules of different developmental stages, including the OsERECTA2 (OsER2) receptor-like kinase gene, were confirmed by in-situ hybridization. We further characterized the OsER2 loss-of-function mutant which had an excessive number of female germline cells and an abnormal female gametophyte, suggesting that OsER2 regulates germline cell specification during megasporogenesis in rice. These results expand our understanding of the molecular control of megasporogenesis in rice and contribute to the functional studies of genes involved in megasporogenesis.

9.
J Pharm Biomed Anal ; 182: 113110, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32004768

RESUMO

Callicarpa nudiflora, belonging to the family Verbenaceae, is widely used to treat inflammation caused by bacterial infection.However, the underlying active substances of C. nudiflora against inflammation remains obscure. In this work, an ultra high-performance liquid chromatography (UHPLC) coupled with quadrupole time-of-flight mass spectrometry method was developed to characterize the ingredients in C. nudiflora, and a validated UHPLC coupled with triple quadrupole tandem mass spectrometry method was applied to quantify major components. As a result, a total of 96 chemical compounds were identified in C. nudiflora, and 26 compounds of them were further quantified in 34 batches of C. nudiflora. Based on the identified components from C. nudiflora, a compound-target network for the anti-inflammation effect was constructed by reverse docking target prediction, disease associated genes screening in DisGeNET and the protein-protein interaction from STRING. The compound-target network showed that C. nudiflora might exert anti-inflammation effect on the target of complement 3 and 5 in the pathway of cells and molecules involved in local acute inflammatory response, and 16 effective candidate compounds were found such as catalpol, acteoside, rutin, etc. This study provided an opportunity to deepen the understanding of the chemical composition and the potential anti-inflammatory mechanism of C. nudiflora.

10.
Gene ; 737: 144411, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32006596

RESUMO

Long non-coding RNAs (lncRNAs) have been identified in cerebral ischemia-reperfusion (I/R) injury nowadays. Herein, we uncovered the function and underlying mechanism of the lncRNA Rian in cerebral I/R injury. The oxygen-glucose deprivation model in N2a cells was offered to mimic cerebral I/R injury in vitro. Trypan blue staining, reactive oxygen species (ROS) production, and caspase-3 activity were used to evaluate cell apoptosis. Then, middle cerebral artery occlusion was conducted to evaluate the function of lncRNA Rian in mice. Real-time PCR and western blotting were performed to determine the expression of lncRNA Rian, miR-144-3p, GATA binding protein 3 (GATA3), caspase-3, Bax, and Bcl-2. The results showed that both Rian and GATA3 were downregulated, and miR-144-3p was upregulated in cerebral I/R injury in vitro and in vivo. Overexpression of Rian could inhibit the cell apoptosis induced by oxygen-glucose deprivation. Furthermore, overexpression of Rian distinctly reduced the infarct size, and it also improved the neurological score. Overexpression of Rian could abolish miR-144-3p-mediated I/R injury in vitro and in vivo. Besides, GATA3 was the target of miR-144-3p and GATA3 could be regulated co-operatively by miR-144-3p and Rian. Consequently, these findings showed that the Rian/miR-144-3p/GATA3 axis is an essential signaling in cerebral I/R injury. The lncRNA Rian may serve as a potential target for novel treatment in patients with ischemic stroke.

11.
Ecotoxicol Environ Saf ; 192: 110255, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32018154

RESUMO

Tetrabromobisphenol A (TBBPA) and its derivatives are the common flame-retardants that may increase the risk of development of many types of cancers, including liver cancer. However, the effects of TBBPA in the development and progression of liver cancer remains unknown. This study investigated the potential effects of TBBPA on a metastatic phenotype of hepatocellular carcinoma cell line-HepG2. Our results revealed that TBBPA significantly promoted the migration and invasion via affecting the number and distribution of lysosomes in HepG2 cells in a dose-dependent manner. Moreover, TBBPA decreased the intracellular protein levels of Beta-Hexosaminidase (HEXB), Cathepsin B (CTSB) and Cathepsin D (CTSD) while increased the extracellular CTSB and CTSD. It entailed that TBBPA exposure could promote the lysosomal exocytosis in cancer cells. The reversal results were obtained after adding lysosomal exocytosis inhibitor vacuolin-1. Docking results suggested that TBBPA could bind to TRPML1. It was consistent with the binding position of agonist ML-SA1. TRPML1 knockdown significantly decreased the invasion and migration, and the results were reversed when TBBPA was added. The results were indicated that TRPML1 was critical in lysosomal exocytosis. In addition, our results showed that TBBPA-TRPML1 complex regulated the calcium-mediated lysosomal exocytosis, thereby promoting the metastasis in liver cancer cells. It was expected that our data could provide important basis for understanding the molecular mechanism(s) of TBBPA promoting invasion and migration of hepatoma cells and give rise to profound concerns of TBBPA exposure on human health.

12.
EuroIntervention ; 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-32038026

RESUMO

AIMS: This analysis presents the final 5-year results of the I-LOVE-IT 2 trial, a noninferiority study comparing BP- sirolimus-eluting stent (SES) with DP-SES in patients with coronary artery disease. METHODS AND RESULTS: Overall, 2737 Chinese patients eligible for coronary stenting were treated with BP- or DP-SES in a 2:1 ratio. Patients who were randomized to BP-SES group were additionally re-randomized to receive either 6-month or 12-month dual antiplatelet therapy (DAPT) in a 1:1 ratio. The primary endpoint was 12-month target lesion failure (TLF: cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization). At five years, overall follow-up rate was 90.8%, and the cumulative incidence of TLF as the primary endpoint was similar between BP-SES and DP-SES (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.79 to 1.28), as was that for patient-oriented composite endpoint (PoCE: all-cause death, all MI and any revascularization) (HR: 1.03, 95% CI: 0.86 to 1.23), or definite/probable ST (HR: 1.11, 95% CI: 0.70 to 1.77). Cumulative events also were similar between 6-month DAPT and 12-month DAPT groups after BP-SES implantation. CONCLUSIONS: I-LOVE-IT 2 has shown that the 5-year safety and efficacy of BP-SES and DP-SES were similar, as were those between 6-month and 12-month of DAPT after BP-SES implantations.

13.
Biochim Biophys Acta Biomembr ; : 183217, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32061646

RESUMO

As the only exposed viral protein at the membrane surface of HIV, envelope glycoprotein gp120 is responsible for recognizing host cells and mediating virus-cell membrane fusion. Available structures of gp120 indicate that it exhibits two distinct conformational states, called closed and open states. Although experimental data demonstrates that CD4 binding stabilizes open state of gp120, detailed structural dynamics and kinetics of gp120 during this process remain elusive. Here, two open-state gp120 simulation systems, one without any ligands (ligand-free) and the other complexed with CD4 (CD4-bound), were subjected to microsecond-scale molecular dynamics simulations following the conformational transitions and allosteric pathways of gp120 evaluated by using the Markov state model and a network-based method, respectively. Our results provide an atomic-resolution description of gp120 conformational transitions, suggesting that gp120 is intrinsically dynamic from the open state to closed state, whereas CD4 binding blocks these transitions. Consistent with experimental structures, five metastable conformations with different orientations of the V1/V2 region and V3 loop have been extracted. The binding of CD4 significantly enhances allosteric communications from the CD4-binding site to V3 loop and ß20-21 hairpin, resulting in high-affinity interactions with coreceptors and activation of the conformational transitions switcher, respectively. This study will facilitate the structural understanding of the CD4-binding effects on conformational transitions and allosteric pathways of gp120.

14.
Perit Dial Int ; : 896860819893812, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-32063196

RESUMO

BACKGROUND: End-stage renal disease has been imposing a heavy economic burden on public health; however, few studies have been performed on the cost-effectiveness of dialysis modalities. We aim to estimate the cost-effectiveness of different dialysis modalities in China. METHODS: Cost-effectiveness analyses were performed using Markov models based on published data of hemodialysis (HD) and peritoneal dialysis (PD) modalities in China. Sensitivity analyses were conducted to identify key variables influencing the results. RESULTS: Over a 10-year time horizon, the base-case cost-effectiveness analysis indicated that PD-first absolutely dominated the HD-first option by gaining 0.13 more quality-adjusted life years (QALYs) and costing RMB ¥81,081 less. When using reported mortality of HD and PD from the United States, the PD-first option still dominated HD-first with higher QALYs and lower costs. Sensitivity analyses revealed that the results were more sensitive to the direct cost of HD, utility of HD, utility of PD, direct cost of PD, PD mortality, and HD mortality, while less sensitive to the indirect costs and transition probabilities. The HD utility needed to be at least 0.148 higher than PD utility for HD to be cost-effective. PD was about 72% likely to be considered cost-effective compared with HD, regardless of the willingness-to-pay for QALYs. CONCLUSION: PD appears to be more cost-effective than HD in China, and the major influential factors on the cost-effectiveness are the direct costs of HD, utility of HD, utility of PD, direct costs of PD, PD mortality, and HD mortality.

15.
Int J Phytoremediation ; : 1-10, 2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32064892

RESUMO

The effects of potassium (K) fertilization (KCl, analytically pure; 0, 60, 200, and 400 mg kg-1) on the growth and Mn accumulation of Camellia oleifera in two types of Mn-contaminated soils were investigated. The potential mechanisms underlying the impacts of K fertilization were explored. C. oleifera accumulated high amounts of Mn in both soil conditions. The addition of K fertilizer decreased the soil pH and promoted Mn accumulation in C. oleifera. However, the plant biomass decreased significantly under the high level of K fertilization (400 mg kg-1), and the oxidative stress was stimulated under Mn contamination. But an appropriate concentration of K fertilizer (200 mg kg-1) was necessary for the formation of photosynthesis pigments, nonenzymatic antioxidants and antioxidant enzymes, metabolic processes, and nutrient uptake. Furthermore, when plants supplemented with a low level of K fertilization (200 mg kg-1), the catalase activity in C. oleifera leaves was enhanced to alleviate oxidative stress and protect the plant from Mn contamination. Our study demonstrated that 200 mg kg-1 of K fertilizer has the potential to further enhance the efficiency of Mn phytoremediation by C. oleifera.

16.
Antiviral Res ; : 104734, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32057770

RESUMO

Hepatitis C virus (HCV) is a leading cause of chronic hepatitis and end-stage liver diseases. Mature HCV virions are bound by host-derived lipoproteins. Lack of an HCV vaccine warrants a major role of antiviral treatment in the global elimination of hepatitis C. Although direct-acting antivirals (DAAs) are replacing the interferon-based treatment and have dramatically improved the cure rate, the presence of viral variants resistant to DAAs, HCV genotype/subtype-specific efficacy, and high cost of DAAs argue novel and affordable regimens. In this study, we identified the antiviral effects of long-chain fatty acyl-coenzyme A (LCFA-CoA) against the infections of HCV genotypes 1-6 through targeting mature HCV-bound lipoproteins, suggesting novel mechanism(s) of antiviral different from those used by host-targeting agents or DAAs. We found that the antiviral activity of LCFA-CoA relied on the long-chain saturated fatty acid and the CoA group, and was enhanced when combined with pegylated-interferon or DAAs. Importantly, we demonstrated that LCFA-CoA efficiently inhibited the infection of HCV variants carrying DAA-resistant mutations. The mechanistic study revealed that LCFA-CoA specifically abolished the attachment and binding steps and also inhibited the cell-to-cell viral transmission. LCFA-CoA targeted mature HCV-bound lipoproteins, but not apolipoproteins B or E. In addition, LCFA-CoA could also inhibit the infection of the dengue virus. Our findings suggest that LCFA-CoA could potentially serve as a supplement HCV therapy, particularly for the DAA-resistant HCV variants. Taken together, LCFA-CoA may be further developed to be a novel class of antivirals with mechanism(s), different from host-targeting agents or DAAs, of targeting the components associated with mature HCV virions.

18.
Curr Microbiol ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060766

RESUMO

A bacterium, designated HX2-24 T, was isolated from activated sludge treating pesticide-manufacturing wastewater. Colonies of the strain on nutrient agar were circular, transparent, and colorless. Strain HX2-24 T shared 98.1% 16S rRNA gene sequence similarity with Extensimonas vulgaris S4T, and less than 97% similarities with other type strains. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the strain formed a clade with E. vulgaris S4T. The major cellular fatty acids were C16:0, summed feature 3 (C16:1ω7c and/or C16:1ω6c) and C17:0 cyclo, the major polar lipids were phosphatidylethanolamine (PE), phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), aminophospholipid (APL), glycophospholipid (GPL), and aminoglycolipid (AGL). The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between HX2-24 T and E. vulgaris S4T were 92% and 41%, respectively. The G + C content of strain HX2-24 T was 64.4 mol%. Thus, based on the phenotypic, chemotaxonomic, and genotypic characteristics, strain HX2-24 T represents a novel species in the genus Extensimonas, for which the name Extensimonas perlucida HX2-24 T sp. nov. is proposed. The type strain is HX2-24 T (= KCTC 72472 T = CCTCC AB 2019178 T).

19.
Respir Med ; 163: 105897, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32056837

RESUMO

BACKGROUND: Although the association between diabetes mellitus (DM) and tuberculosis (TB) has been well-documented for centuries, evidence of the link between diabetes and drug resistance among previously treated TB patients remains limited and inconsistent. METHODS: An observational study was performed that involved 1791 retreated TB-no DM patients (refers to TB cases without diabetes) and 93 retreated TB-DM patients (refers to TB cases with diabetes) in Shandong, China from 2004 to 2017. Baseline data including demographic and clinical characteristics, drug susceptibility test (DST) results, and diabetes status were collected. Categorical baseline characteristics were compared by Fisher's exact or Pearson Chi-square test. Univariable analysis and multivariable logistic models were used to estimate the association between diabetes and different drug resistance profiles. RESULTS: Retreated TB-DM patients have a higher rate of drug resistance than TB-no DM patients (34.41% vs 25.00%, P < 0.01). Diabetes co-morbidity was significantly associated with any drug-resistant tuberculosis (DR-TB, odds ratio (OR):1.56, 95% confidence interval (CI): 1.01-2.43), multidrug resistant tuberculosis (MDR-TB, OR: 2.48, 95%CI:1.39-4.41; adjusted OR (aOR):2.94, 95%CI:1.57-5.48), isoniazid-related resistance (OR:1.71, 95%CI:1.04-2.81), rifampin-related resistance (OR:2.56, 0.54, 95%CI: 1.54-4.26; aOR:2.69, 95%CI:1.524-4.74), isoniazid + rifampin resistance (OR: 3.55, 95%CI:1.33-9.44; aOR:4.13, 95%CI:1.46-11.66), any resistance to isoniazid + streptomycin (OR:2.34, 95%CI:1.41-3.89; aOR:2.22, 95%CI:1.26-3.94), and any resistance to rifampin + isoniazid (OR:2.48, 95%CI:1.39-4.41; aOR:2.94, 95%CI: 1.57-5.48), compared with pan susceptible TB cases, P < 0.05. CONCLUSIONS: The risk of acquired drug resistance increased significantly among retreated TB-DM patients compared with retreated TB-no DM patients, underlining the necessity of more interventions during the clinical management of TB-DM cases.

20.
Biomed Pharmacother ; 125: 109947, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32058215

RESUMO

PURPOSE: 99mTc-duramycin imaging enables specific visualization of cell death qualitatively and quantitatively. This study aimed to investigate the potential of 99mTc-duramycin imaging in the early prediction of the curative effect of radiotherapy in combination with or without cetuximab in a nasopharyngeal carcinoma (NPC) model. METHODS: Male BALB/c mice bearing NPC xenografts were randomized into four groups (six mice each group). Group 1 received radiotherapy (RT, 15 Gy/mouse) in combination with cetuximab (CTX, 2 mg/mouse), group 2 received RT (15 Gy/mouse), group 3 was treated using CTX (2 mg/mouse), and group 4, the control group, was treated using a vehicle. 99mTc-duramycin imaging was performed before treatment and 24 h after treatment to evaluate tumor response. Tumor uptake of 99mTc-duramycin was validated ex vivo using γ-counting. Treatment response was further validated by cleaved caspase-3 (CC3) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL). Another four groups were treated parallelly under the same conditions to observe treatment response by tumor volume changes. RESULTS: After 24 h treatment, 99mTc-duramycin uptake in the NPC tumor models were significantly higher in group 1 than in group 2 (P < 0.05), group 3 (P < 0.05), or group 4 (P < 0.05); the uptake also increased notably in comparison with baseline values (P < 0.05). Compared with group 4, group 2 and group 3 both showed significant 99mTc-duramycin uptake in the tumors (P < 0.05). Although the 99mTc-duramycin uptake of group 2 was moderately higher than group 3, there were no significant differences between these two groups (P >0.05). There was a strong positive correlation between tumor 99mTc-duramycin uptake and CC3 (r = 0.893, p < 0.0001) and TUNEL (r = 0.918, P < 0.0001). Tumor volume decreased remarkably in the RT in combination with CTX group on day 5, in the RT alone group on day 7, and was inhibited on day 8 in the CTX alone group, whereas the tumors grew continuously in the control group. CONCLUSIONS: We demonstrated that RT in combination with CTX treatment significantly improved disease control in a NPC xenograft model compared with monotherapy with either. 99mTc-duramycin imaging might be able to reliably identify response to RT in combination with CTX as early as 24 h after therapy initiation in NPC xenograft models. This might help to isolate non-responding patients in a timely manner and avoid unnecessary side effects in the clinic in the future.

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